Microsoft word - drg pubs_0608.doc

Diabetes Research Group
(Publications 2001-)
REVIEWS AND BOOK CHAPTERS
McClenaghan, N.H. and Flatt, P.R. Hormones of the endocrine pancreas. In: Encyclopedia of Food Sciences and Nutrition, Eds. B. Caballero, L. Trugo and P. Finglas, 2nd Edn., Academic Press, London, pp. 3150-3157, 2003. Bailey, C.J. and Flatt, P.R. Animal syndromes resembling type 2 diabetes. In: Textbook of Diabetes, Eds. J.C. Pickup and G. Williams, 3rd Edn., Blackwell Scientific Publications, Oxford, pp 25.1-25.30, 2003. Flatt, P.R. The hormonal and neural control of endocrine pancreatic function. In: Textbook of Diabetes, Eds. J.C. Pickup and G. Williams, 3rd Edn., Blackwell Scientific Publications, Oxford, pp 11.1-11.21, 2003. Gault, V.A., Flatt, P.R. and O’Harte, F.P.M. Glucose-dependent insulinotropic polypeptide (GIP): anti-diabetic and anti-obesity potential. Neuropeptides 37: 253-263; 2003 . Gault, V.A., Flatt, P.R. and O’Harte, F.P.M. Glucose-dependent insulinotropic polypeptide analogues and their therapeutic potential for the treatment of obesity-diabetes. Biochem. Biophys. Res. Comm. 308: 207-213; 2003. Furman, B.L., Pyne, N., Flatt, P.R. and O’Harte, F.P.M. Targeting beta cell cyclic adenosine monophosphate for the development of novel drugs for type 2 diabetes mellitus. J. Pharm. Pharmacol., 56: 1-16; 2004. Green, B.D., Gault, V.A., O’Harte, F.P.M. and Flatt, P.R. Structurally modified analogues of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) as future antidiabetic agents. Curr. Pharm. Des. 10: 3651-3662; 2004 Green, B.D., Irwin, N., Gault, V.A., O’Harte, F.P.M. and Flatt, P.R. Development and therapeutic potential of incretin hormone analogues for type 2 diabetes. Br. J. Diab. Vasc. Dis. 5: 134-140; 2005. Green, B.D., Flatt, P.R. and Bailey, C.J. Inhibition of dipeptidyl peptidase IV activity as potential therapy of type 2 diabetes mellitus. Expert Opin. Investig. Drugs, 11: 525-539; 2006. Conlon, J.M., Patterson, S. and Flatt, P.R. Major contributions of comparative endocrinology to the development and exploitation of the incretin concept. J. Exp. Zoolog. A Comp. Exp. Biol. 305: 781-786; 2006. Flatt, P.R. and Green, B.D. Nutrient regulation of insulin secetion in diabetes: Problems and potential solutions. Biochem. Soc. Trans. 34: 774-778; 2006. Green, B.D., Flatt, P.R. and Bailey, C.J. Dipeptidyl peptidase IV (DPPIV) inhibitors: A newly emerging drug class for the treatment of type 2 diabetes. Diab. Vasc. Dis. Res. 3: 159-165; 2006. Green, B.D., Flatt, P.R. and Bailey, C.J. Gliptins: dipeptidyl peptidase-4 (DPP-4) inhibitors to treat type 2 diabetes. Future Prescriber 8: 7-13; 2007. Flatt, P.R. Effective surgical treatment of obesity may be mediated by ablation of the lipogenic gut hormone gastric inhibitory polypeptide (GIP): Evidence and clinical opportunity for development of new obesity-diabetes drugs? Diab. Vasc. Dis. Res. 4: 151-153; 2007. Green, B.D. and Flatt, P.R. Incretin hormone mimetics and analogues in diabetes therapeutics. Best Pract. Res. Clin. Endocrinol. Metab. 21: 497-516; 2007. Flatt, P.R., Bailey, C.J and Green B.D. Dipeptidyl peptidase IV (DPPIV) and related molecules in type 2 diabetes. Front. Biosci. 13: 3648-3660; 2008. McKillop, A.M. and Flatt, P.R. Recent developments in the search for biomarkers for the diagnosis and monitoring of diabetes. Recent Patents on Endocrine, Metabolic and Immune Drug Discovery (in press). Flatt, P.R. Gastric inhibitory polypeptide (GIP) revisited – a new therapeutic target for obesity-diabetes? Diabetic Med. (in press). Diabetes Research Group
(Publications 2001-)
FULL SCIENTIFIC PAPERS
McClenaghan, N.H., Ball, A. and Flatt, P.R. Prolonged exposure to tolbutamide specifically desensitises sulphonylurea but not imidazoline-induced insulin release. Biochem. Pharmacol., 61: 527-536; 2001. O’Harte, F.P.M., Mooney, M.H., Kelly, C.M.N., McKillop, A.M. and Flatt, P.R. Degradation and glycaemic effects of His7-glucitol glucagon-like peptide-1 (7-36)amide in obese diabetic ob/ob mice. Reg. Peptides, 96: 95-104; 2001. Hamid, M., McCluskey, J.T., McClenaghan, N.H. and Flatt, P.R. Comparative functional study of clonal insulin-secreting cells cultured in five commercially available tissue culture media. Cell Transplant., 10: 153-159; 2001. Hamid, M., McCluskey, J.T., McClenaghan, N.H. and Flatt, P.R. Functional examination of microencapsulated clonal insulin-secreting beta-cells Cell Biol. Int. 25: 553-556; 2001. Picton, S.F., Flatt, P.R. and McClenaghan, N.H. Differential acute and long-term actions of succinic acid monomethyl ester exposure on insulin secreting cells. Int. J. Exper. Diab. Res., 2: 19-27; 2001. Davies, E., Abdel-Wahab, Y.H.A., Flatt, P.R. and Bailey, C.J. Functional enhancement of electrofusion-derived BRIN-BD11 cells insulin-secreting cells after implantation into diabetic mice. Int. J. Exper. Diab. Res., 2: 29-36; 2001. 3.0 McKillop, A.M., Mooney, M.H., McCluskey, J.T., Abdel-Wahab, Y.H.A., Harriott, P., O’Harte, F.P.M. and Flatt, P.R. Evaluation of glycated insulin in pancreas and circulation of diabetic animal models using immunocytochemistry and a novel and specific radioimmunoassay. Biochem. Biophys. Res. Commun. 286: 524-528; 2001. Mooney, M.H., Abdel-Wahab, Y.H.A., Morgan, L.M., O’Harte, F.P.M. and Flatt, P.R. Detection of glycated gastric inhibitory polypeptide within the intestines of diabetic-obese (ob/ob) mice. Endocrine, 16: 167-171; 2001. Abdel-Wahab, Y.H.A., O'Harte, F.P.M., Barnett, C.R. and Flatt, P.R. Effects of vitamin C supplementation on insulin glycation and glucose homeostasis in obese hyperglycaemic (ob/ob) mice. Metabolism, 51: 514-517; 2002. Furman, B.L. and Flatt, P.R. Report of the 11th EASD Islet Group meeting. Glasgow, UK, 13-15 September 2001. Diabetologia. 45: R26-R29; 2002. Conroy, S.J., Green, I.C., Byrne, P.M., Nolan, J., Flatt, P.R. and Newsholme, P. Evidence for a sustained increase in clonal beta cell intracellular Ca2+ levels after incubation in the presence of newly diagnosed type-1 diabetic patient sera. Possible role in serum-induced inhibition of insulin secretion. J. Endocrinol., 173: 53-62; 2002. Mooney, M.H., Abdel-Wahab, Y.H.A., McKillop, A.M., O’Harte, F.P.M. and Flatt, P.R. Evaluation of glycated glucagon-like peptide-1(7-36)amide in intestinal tissue of normal and diabetic animal models. Biochem. Biophys. Acta, 1569: 75-80; 2002. Van Eylen F., Horta, O.D., Barez, A., Kamagate A., Flatt, P.R., Macianskiene, R., Mubagwa, K. and Herchuelz, A. Overexpression of the Na/Ca exchanger shapes stimulus-induced cytosolic Ca2+ oscillations in insulin-producing BRIN-BD11 cells. Diabetes 51: 366-375; 2002. Gault, V.A., O’Harte, F.P.M., Harriott, P. and Flatt, P.R. Characterisation of the cellular and metabolic effects of a novel enzyme-resistant antagonist of glucose-dependent insulinotropic polypeptide. Biochem. Biophys. Res. Comm. 290: 1420-1426; 2002. Miguel, J.C., Abdel-Wahab, Y.H.A., Mathias, P.C. and Flatt, P.R. Muscarinic receptor subtypes mediate stimulatory and paradoxical inhibitory effects on an insulin-secreting beta cell line. Biochim. Biophys. Acta, 1569: 45-50; 2002. O’Harte, F.P.M., Gault, V.A., Parker, J.C., Harriott, P., Mooney, M.H., Bailey, C.J. and Flatt, P.R Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP. Diabetologia, 45: 1281-1291; 2002. Brennan, L., Shine, A., Hewage, C., Malthouse, J.P.G., Brindle, K.M., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. A NMR based demonstration of substantial oxidative L-alanine metabolism and L-alanine enhanced glucose metabolism in a clonal pancreatic beta cell line – Metabolism of L-alanine is important to the regulation of insulin secretion. Diabetes, 51: 1714-1721; 2002. Hamid, M., McCluskey, J.T., McClenaghan, N.H. and Flatt, P.R. Comparison of the secretory properties of four insulin-secreting cell lines. Endocrine Res., 28: 35-47; 2002. Gault, V.A., Flatt, P.R., Bailey, C.J., Harriott, P., Greer, B., Mooney, M.H. and O’Harte, F.P.M. Enhanced cyclic AMP generation and insulin-releasing potency of two novel Tyr1-modified enzyme resistant forms of GIP, is associated with significant antihyperglycaemic activity in spontaneous obestity-diabetes. Biochem. J., 367: 913-920; 2002. McKillop, A.M., Abdel-Wahab, Y.H.A., Mooney, M.H., O’Harte, F.P.M. and Flatt, P.R. Secretion of glycated insulin from pancreatic beta cells in diabetes represents a novel aspect of beta cell dysfunction and glucose toxicity. Diabete Metab., 28: 3S61-3S69; 2002. Gault, V.A., Harriott, P., Flatt, P.R. and O’Harte, F.P.M. Cyclic AMP production and insulin releasing activity of synthetic fragment peptides of glucose-dependent insulinotropic peptide. Biosci. Rep., 22: 523-528; 2002. Picton, S.F., McCluskey, J.T., Flatt, P.R. and McClenaghan, N.H. Effects of cytotoxic agents on functional integrity and ontioxidant enzymes in clonal beta cells. Diabete Metab., 28: 3S70-3S77; 2002. Gault, V.A., Parker, J.C., Harriott, P., Flatt, P.R. and O’Harte, F.P.M. Evidence that the major degradation product of glucose-dependent insulinotropic polypeptide (GIP), GIP(3-42), is a GIP receptor antagonist in vivo. J. Endocrinol., 175: 525-533; 2002. Gault, V.A., Flatt, P.R., Bailey, C.J., Harriott, P., Greer, B., Mooney, M.H. and O’Harte, F.P.M. Improved biological activity of Gly2 and Ser2 substituted analogs of glucose-dependent insulinotropic polypeptide. J. Endocrinol., 176: 133-141; 2003. Miguel, J.C., Abdel-Wahab, Y.H.A., Green, B.D., Mathias, P.C. and Flatt, P.R. Cooperative enhancement of insulinotropic action of GLP-1 by acetylcholine uncovers paradoxical inhibitory effect of beta cell muscarinic receptor activation on adenylate cyclase activity. Biochem. Pharmacol., 65: 283-292; 2003. Gault, V.A., Irwin, N., Harriott, P., Flatt, P.R. and O’Harte, F.P.M. DPP IV resistance and insulin releasing activity of a novel di-substituted analogue of glucose-dependent insulinotropic polypeptide, (Ser2-Asp13)GIP. Cell Biol. International, 27: 41-46; 2003. Hunter, S.J., Boyd, A.C., O’Harte, F.P.M., McKillop, A.M., Wiggan, M.I., Ennis, C.N., Gamble, R., Sheridan, B., Barnett, C.R., McNulty, H., Bell, P.M. and Flatt, P.R. Demonstration of glycated insulin in human diabetic plasma and decreased biological activity by euglycemic clamp technique in man. Diabetes, 52: 492-498; 2003. Gallagher, A.M., Duffy, G., Flatt, P.R and Abdel-Wahab, Y.H.A. The effects of traditional antidiabetic plants on in vitro glucose diffusion. Nutr. Res. 113: 413-424; 2003. McKillop, A.M., Meade A., Flatt, P.R. and O’Harte, F.P.M. Evaluation of the site(s) of glycation in human proinsulin by ion-trap LCQ-electrospray ionization masss spectrometry. Reg. Peptides 113: 1-8; 2003. Lindsay, J.R., McKillop, A.M., Mooney, M.H., Flatt, P.R., Bell, P.M. and O’Harte, F.P.M. Meal-induced twenty-four hour profile of circulating insulin in type 2 diabetic subjects. Metabolism 52: 631-635; 2003. Lindsay, J.R., McKillop, A.M., Mooney, M.H., O’Harte, F.P.M., Bell, P.M. and Flatt, P.R. Demonstration of elevated concentrations of circulating glycated insulin in human type 2 diabetes using a novel and specific radioimmunoassay. Diabetologia 46: 475-478; 2003. Gault, V.A., O’Harte, F.P.M., Harriott, P. and Flatt, P.R. Degradation, cyclic AMP production, insulin secretion and glycaemic effects of two novel N-terminal Ala2-substituted analogues of GIP with preserved biological activity in vivo. Metabolism 52: 679-687; 2003. Gault, V.A., O’Harte, F.P.M., Harriott, P., Mooney, M.H., Green, B.D. and Flatt, P.R. Effects of the novel (Pro3)GIP antagonist and exendin(9-39) on GIP- and GLP-1-induced cAMP gerneration, insulin secretion and postprandial insulin release in obese diabetic ob/ob mice: Evidence that GIP is the major physiological incretin. Diabetologia, 46: 222-2320; 2003. Gault, V.A., Flatt, P.R. and O’Harte, F.P.M. Glucose-dependent insulinotropic polypeptide analogues and their therapeutic potential for the treatment of obesity-diabetes. Biochem. Biophys. Res. Comm. 308: 207-213; 2003. Brennan, L., Corless, M., Hewage, C., Malthouse, J.P.G., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. 13C NMR Analysis reveals a link between L-glutamine metabolism, L-glutamate concentration and γ-glutamyl cycle activity in a clonal pancreatic beta cell line. Diabetologia, 46: 1512-1521; 2003. Lindsay, J.R., McKillop, A.M., Mooney, M.H., O’Harte, F.P.M., Flatt, P.R. and Bell, P.M. Nateglinide effects on the secretion of glycated insulin and glucose tolerance in Type 2 diabetes. Diabetes. Res. Clin. Pract., 61: 167-173; 2003. Gault, V.A., Flatt, P.R. and O’Harte, F.P.M. Glucose-dependent insulinotropic polypeptide (GIP): anti-diabetic and anti-obesity potential. Neuropeptides, 37: 253-263; 2003. Green, B.D., Mooney, M.H., Gault, V.A., Bailey, C.J., Irwin, N., Harriott, P., Greer, B., Flatt, P.R. and O’Harte, F.P.M. Novel DPP IV resistant analogues of GLP-1 with potent insulinotropic activity in vitro conferring improved glucose-lowering action in vivo. J. Mol. Endocrinol., 31: 529-540; 2003. Dixon, G., Nolan, J., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. A comparative study of nutrient consumption by rat islet cells and the clonal beta-cell line BRIN-BD11 – the functional significance of L-alanine. J. Endocrinol., 179: 447-454; 2003. Green, B.D., Mooney, M.H., Gault, V.A., Bailey, C.J., Irwin, N., Harriott, P., Greer, B., Flatt, P.R. and O’Harte, F.P.M. Metabolic stability, receptor binding, cyclic AMP generation, insulin secretion and antihyperglycaemic activity of novel N-terminal (Glu9)-substituted analogues of glucagon-like peptide-1. Biological Chemistry 384: 1543-1551; 2003 Marenah, L., Orr, D.F., McClean, S., Flatt, P.R., Shaw, C. and Abdel-Wahab, Y.H.A. Isolation and characterisation of a novel class of insulinotropic peptides in the skin of the frog Agalychnis litodryas. Reg. Peptides, 120: 33-38; 2004. Lees Murdock, D.J., Clarke, J., Flatt, P.R., Barnett, Y.A. and Barnett, C.R. Role of CYP2E1 in ketone-stimulated insulin release in pancreatic B-cells. Biochem. Pharmacol., 67: 875-884; 2004. Marenah, L., McClean, S., Orr, D.F., Flatt, P.R., Shaw, C. and Abdel-Wahab, Y.H.A. Novel insulin-releasing peptides in the skin of Phyllomedusa trinitatis frog include 28 amino acid peptide from dermaseptin BIV precursor Pancreas., 29: 110-115; 2004. Green, B.D., Mooney, M.H., Gault, V.A., Bailey, C.J., Irwin, N., Harriott, P., Greer, B., Flatt, P.R. and O’Harte, F.P.M. N-terminal His7-modification of GLP-1 generates DPP IV-stable analogues with potent antihyperglycaemic activity. J. Endocrinol., 180: 379-388; 2004. Miguel J.C., Abdel-Wahab, Y.H.A., Mathias, P.C.F. and Flatt, P.R. Time-correlation between membrane depolarization and intracellular calcium in insulin-secreting BRIN-BD11 cells: Studies using FLIPR. Cell Calcium 36: 43-50; 2004. Green, B.D., Mooney, M.H., Gault, V.A., Bailey, C.J., Irwin, N., Harriott, P., Greer, B., Flatt, P.R. and O’Harte, F.P.M. Lys9 for Glu9 substitution in glucagon-like peptide-1(7-36)amide (GLP-1) confers DPP IV resistance with cellular and metabolic actions similar to those of established antagonists GLP-1(9-36)amide and exendin (9-39). Metabolism, 53: 252-259; 2004. Marenah, L., Orr, D.F.,. McClean, S., Flatt, P.R., Shaw, C. and Abdel-Wahab, Y.H.A. Brevinin-1 and multiple insulin-releasing peptides in the skin of the frog Rana palustris. J. Endocrinol. 181: 347-354; 2004. Green, B.D., Mooney, M.H., Gault, V.A., Bailey, C.J., Irwin, N., Harriott, P., Greer, B., Flatt, P.R. and O’Harte, F.P.M. Degradation, receptor binding, insulin secreting and antihyperglycaemic actions of palmitate derivitised native and Ala8-substituted GLP-1 analogues. Biological Chemistry 385: 169-177; 2004. Dixon, G., Nolan, J., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. Arachidonic acid, palmitic acid and glucose are important for the modulation of clonal pancreatic breta cell insulin secretion, growth and viability. Clin. Science, 106: 191-199; 2004. Liu, H-K., Green, B.D., Gault, V.A., McCluskey, J.T., McClenaghan, N.H., O'Harte, F.P.M. and Flatt, P.R. N-acetyl-GLP-1: a DPP IV resistant analogue of glucagon-like peptide-1 (GLP-1) with improved effects on pancreatic beta-cell associated gene expression. Cell Biol. Int. 28: 69-73; 2004. Marenah L, Orr D.F, McClean S, Shaw, C., Flatt P.R and Abdel-Wahab Y.H.A Skin secretions of Bombina variegata frog contain multiple insulin releasing peptides including bombesin and entirely novel insulinotropic structures. Biological Chemistry 385: 315-321; 2004. Ball, A.J., McCluskey, J.T., Flatt, P.R. and McClenaghan, N.H. Chronic exposure to tolbutamide and glibenclamide impairs insulin secretion but not expression of K-ATP channel components. Pharmac. Res. 50: 41-46; 2004. Liu, H-K., Green, B.D., McClenaghan, N.H., McCluskey, J.T. and Flatt, P.R. Long-term beneficial effects of vanadate, tungstate and molybdate on insulin secretion and function of cultured beta cells. Pancreas, 28: 364-368; 2004. Ball, A.J., Flatt, P.R. and McClenaghan, N.H. Acute and long-term effects of nateglinide on insulin secretory pathways. Br. J Pharmacol. 142: 367-373; 2004. Liu, H-K., Green, B.D., Flatt, P.R., McClenaghan, N.H. and McCluskey, J.T. Effects of long-term exposure to nicotinamide and sodium butyrate on growth, viability and the function of clonal insulin-secreting cells. Endocrine Res. 30: 61-68; 2004. Green, B.D., Gault, V.A., Flatt, P.R., Harriott P., Greer, B. and O’Harte, F.P.M. Comparative effects of GLP-1 and GIP on cAMP production, insulin secretion and in vivo antidiabetic actions following substitution of Ala8/Ala2 for 2-aminobutyric acid. Arch. Biochem. Biophys. 428: 136-43; 2004. Irwin N., Gault, V.A., Green, B.D., Greer, B., McCluskey, J.T., Harriott, P., O’Harte, F.P.M. and Flatt, P.R. Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice. Biol. Chem. 385: 845-852; 2004. Furman, B.L., Pyne, N., Flatt, P.R. and O’Harte, F.P.M. Targeting beta cell cyclic adenosine monophosphate for the development of novel drugs for type 2 diabetes mellitus. J. Pharm. Pharmacol., 56: 1-16; 2004. Green, B.D., Gault, V.A., O’Harte, F.P.M. and Flatt, P.R. Structurally modified analogues of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) as future antidiabetic agents. Curr. Pharm. Des. 10: 3651-3662; 2004 Ball, A.J., Flatt, P.R. and McClenaghan, N.H. Alterations of insulin secretion following long-term manipulation of ATP-sensitive potassium channels by diazoxide and nateglinide. Biochem. Pharmacol., 69: 59-63; 2005. Graham, C., Irvine, A.E., McClean, S., Richter, S., Lapin, T.R.J., Flatt, P.R. and Shaw, C. Peptide tyrosine arginine, a potent immunomodulatory peptide isolated and structurally characterised from the skin secretions of the dusky gopher frog, Rana servosa. Peptides, 26: 737-743; 2005. Lindsay, J.R., Duffy, N., McKillop, A.M., Ardill, J., Flatt, P.R. and Bell, P.M. Inhibition of dipeptidyl peptidase IV (DPPIV) activity by oral metformin in type 2 diabetes. Diabetic Med., 22: 654-657; 2005. Irwin, N., Green, B.D., Gault, V.A., Greer, B., Harriott, P., Bailey, C.J., Flatt, P.R. and O’Harte, F.P.M. Degradation, insulin secretion and antihyperglycaemic actions of two palmitate-derivatised N-terminal pyroglutamyl analogues of glucose-dependent insulinotropic polypeptide (GIP). J. Med. Chem. 48: 1244-1250; 2005. Green, B.D., Lui, H.K., McCluskey, J.T., Duffy, N.A., O’Harte, F.P.M., McClenaghan, N.H. and Flatt, P.R. Function of long-term GLP-1 treated pancreatic beta cells is improved by preventing DPP IV mediated degradation of GLP-1. Diabetes, Obesity Metab. 7: 563-569; 2005. Green, B.D., Irwin, N., Gault, V.A., Bailey, C.J., O’Harte, F.P.M. and Flatt, P.R. Chronic treatment of ob/ob mice with exendin(9-39) suggests a minor role of endogenous GLP-1 in metabolic abnormalities of obesity-diabetes. J. Endocrinol., 185: 307-317; 2005. Marenah L, Shaw C, Orr D.F, McClean S, Flatt P.R and Abdel-Wahab Y.H.A Characterisation of naturally occurring peptides in the skin secretion of Rana pipiens frog reveal pipinin-1 as novel insulin releasing agent: J. Peptide Res. 66: 204-210; 2005. Gault, V.A., Irwin, N., Green, B.D., McCluskey, J.T., Greer, B., Bailey, C.J., Harriott, P., O’Harte, F.P.M. and Flatt, P.R. Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3)GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalitities of islet structure in obestity-diabetes. Diabetes 54: 2436-2446; 2005. Green, B.D., Gault, V.A., O’Harte, F.P.M. and Flatt, P.R. A comparison of the cellular and biological properties of DPP IV-resistant N-glucitol analogues of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Diabetes, Obesity Metab. 7: 595-604; 2005. Abdel-Wahab, Y.H.A., Marenah, L., Orr, D.F., Shaw, C. and Flatt, P.R. Isolation and structural characterisation of a novel 13 amino acid insulin-releasing peptide from the skin secretions of Agalychnis calcarifer. Biol Chem. 386: 581-587; 2005. Irwin, N., Green, B.D., Mooney, M., Greer, B., Harriott, P., Bailey, C.J., Gault, V.A., O’Harte, F.P.M. and Flatt, P.R. A novel long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) suitable for once daily administration in type 2 diabetes. J. Pharmacol. Exp. Ther. 314: 1187-1194; 2005. Cunningham, G., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. L-alanine induces changes in metabolic and signal transduction gene expression in a clonal pancreatic beta-cell line and protects from proinflammatory cytokine-induced apoptosis. Clin. Science, 109: 447-455; 2005. Marenah, L., Flatt, P.R., Orr, D.F., Shaw, C. and Abdel-Wahab, Y.H.A. Isolation and structural characterisation of novel Rugosin-A like insulinotropic peptide from the skin secretions of Rana saharica frog. Peptides 26: 2117-2123; 2005. Irwin, N., Gault, V.A., Green, B.D., Greer, B., Harriott, P., Bailey, C.J.,Flatt, P.R. and O’Harte, F.P.M. Antidiabetic potential of two novel fatty acid derivatised, N-terminally modified analogues of glucose-dependent insulinotropic polypeptide (GIP): N-AcGIP(LysPAL16) and N-AcGIP(LysPAL37). Biol. Chem. 386: 679-687; 2005. Liu, H-K., Green, B.D., McClenaghan, N.H., McCluskey, J.T. and Flatt, P.R. Deleterious effects of dehydroepiandrosterone sulphate and dexamethasone on rat insulin- secreting cells under in vitro culture condition. Bioscience Rep. 26: 31-38; 2006. Liu, H-K., Green, B.D., McClenaghan, N.H., McCluskey, J.T. and Flatt, P.R. Deleterious effects of dehydroepiandrosterone sulphate and dexamethasone on rat insulin- secreting cells under in vitro culture condition. Bioscience Rep. 26: 31-38; 2006. McKillop, A.M., Lindsay, J.R., Au, S., Mahood, K.I., O’Harte, F.P.M., Flatt, P.R. and Bell, P.M. Meal-dependent regulation of circulating glycated insulin in type 2 diabetic subjects. Horm. Metabol. Res. 38: 94-97; 2006. Irwin, N., Green, B.D., Gault, V.A., O’Harte, F.P.M., Harriott, P and Flatt, P.R. Effects on glucose homeostasis and insulin secretion of short term up-regulation of the glucose dependent insulinotropic polypeptide (GIP) receptor by N-AcGIP(Lys PAL37) in normal mice. Peptides 27: 893-900; 2006. Mathews, J.N., Flatt, P.R. and Abdel-Wahab, Y.H.A., Asparagus adscendens (Shewta musali) stimulates insulin secretion, insulin action and inhibits starch digestion. Br J Nutr. 95: 576-581; 2006. Marenah, L., Flatt, P.R., Orr, D.F., Shaw, C. and Abdel-Wahab, Y.H.A. Skin secretions of Rana saharica frogs reveal antimicrobial peptides Esculentins-1 and 1B and Brevinins-1E and 2EC with novel insulin releasing activity: J. Endocrinol. 188: 1-9; 2006. Patterson, S., Flatt, P.R., Brennan, L., Newsholme, P. & McClenaghan, N.H. Detrimental actions of metabolic syndrome risk factor, homocysteine, on insulin secretion and pancreatic beta cell glucose metabolism. J. Endocrinol. 189: 301-310; 2006. Irwin, N., O’Harte, F.P.M ., Gault, V.A., Mooney, M.H., Green, B.D., Greer, B., Harriott, P., Bailey, C.J. and Flatt, P.R. Development and characterization of novel long-acting fatty acid derivatised analogs of glucose-dependent insulinotropic polypeptide (GIP) with improved antidiabetic potential. J. Med. Chem. 49: 1047-1054; 2006. Graham, C., Richter, S.C., O’Kane, E., Flatt, P.R. and Shaw, C. Histamine-releasing and antibacterial peptides from the skin secretions of the dusky gopher frog, Rana sevosa. Peptides, 27: 1313-1319; 2006. Green, B.D., Irwin, N., Gault, V.A., O’Harte, F.P.M. and Flatt, P.R. Pituitary adenylate cycles activating protein (PACAP): Assessment of dipeptidyl peptidase IV degradation, insulin releasing activity and antidiabetic potential. Peptides, 27: 1349-1358; 2006. Irwin, N., Green, B.D., Gault, V.A., Harriott, P., O’Harte, F.P.M. and Flatt, P.R. Stable agonist of glucose-dependent insulinotropic polypeptide (GIP) restores pancreatic beta cell glucose responsiveness but not normal glucose tolerance in aging mice. Exp. Gerontology 41: 151-156; 2006. Alana, I., Parker, J.C., Gault, V.A., Flatt, P.R., O’Harte, F.P.M., Malthouse, J.P.G. and Hewage, C. NMR and alanine scan studies of glucose-dependent insulinotropic polypeptide. J. Biol. Chem. 281: 16370-16376; 2006. Hannan, J.M.A., Marenah, L., Ali, L., Rokeya, B., Flatt, P.R. and Abdel-Wahab, Y. Ocimum sanctum leaf extracts stimulate insulin secretion from perfused pancreas, isolated islets and clonal beta cells. J. Endocrinol. 189:127-136; 2006. Irwin, N., Green, B.D., Parker, J.C., Gault, V.A., O’Harte, F.P.M. and Flatt, P.R. Biological activity and antidiabetic potential of synthetic fragment peptides of glucose-dependent polypeptide, GIP(1-16) and (Pro3)GIP(1-16). Reg Peptides, 135: 45-53; 2006. Patterson, S., Flatt, P.R. and McClenaghan, N.H. Homocysteine and other structurally diverse amino thiols can alter pancreatic beta cell function without evoking cellular damage. Biochem. Biophys. Acta, 189: 301-310; 2006. Conlon, J.M., Patterson, S. and Flatt, P.R. Major contributions of comparative endocrinology to the development and exploitation of the incretin concept. J. Exp. Zoolog. A Comp. Exp. Biol. 305: 781-786; 2006. Green, B.D., Lavery, K.S., Irwin, N., O’Harte, F.P.M., Harriott, P., Greer, B., Bailey, C.J. and Flatt, P.R. Novel GLP-1 analogue, (Val8)GLP-1, results in significant improvements of glucose tolerance and pancreatic beta cell function after 3 weeks daily administration in obese diabetic (ob/ob) mice. J. Pharmacol. Exp. Therap. 318: 914-921; 2006. Marenah, L., McCluskey, J.T., Abdel-Wahab, Y.H.A., O’Harte, F.P.M., McClenaghan, N.H. and Flatt, P.R. Stable analogue of glucose-dependent insulinotropic polypeptide, GIP(LysPAL16), enhances functional differentiation of mouse embryonic stem cells into cells expressing specific islet genes and hormones. Biol. Chem. 387: 941-947; 2006. Hannan, J.M.A., Ali, L., Khaleque, J., Akhter M., Flatt, P.R. and Abdel-Wahab, Y. Aqueous extract of Platago ovata husk reduces hyperglycaemia in type 1 and type 2 diabetes by inhibition of intestinal glucose absorption. Br. J. Nutr. 96: 131-137; 2006. Green, B.D., Irwin, N., Cassidy, R.S. and Flatt, P.R. Long-term administration of PACAP receptor antagonist, PACAP(6-27) impairs glucose tolerance and insulin sensitivity in obese diabetic (ob/ob) mice. Peptides 27: 2343-2349; 2006. McClenaghan N.H., Flatt, P.R. and Ball, A.J. GLP-1 augments K-ATP channel-dependent and -independent actions of glucose, sulphonylureas and nateglinide. J. Endocrinol. 190: 889-896; 2006. Irwin, N., Clarke, G., Green, B.D., Greer, B., Harriott, P., Gault, V.A., O’Harte, F.P.M. and Flatt, P.R. Evaluation of the antidiabetic activity of DPP-IV resistant N-terminally modified versus mid-chain acylated analogues of glucose-dependendent insulinotropic polypeptide. Biochem. Pharmac. 72: 719-728; 2006. Green, B.D., Duffy, N.A., Gault, V.A., O’Harte, F.P.M. and Flatt, P.R. Inhibition of dipeptidyl peptidase –IV (DPP IV) activity by metformin enhances the antidiabetic effects of glucagons-like peptide-1 (GLP-1). Eur. J. Pharmacol. 547: 192-199; 2006 Corless, M., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. Glutamine regulates expression of key transcription factor, signal transduction, metabolic gene and protein expression in a clonal pancreatic beta cell line. J. Endocrinol. 190: 719-727; 2006. Brennan, L., Hewage, C., Malthouse, J.P.G., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. Investigating the effects of glibenclamide and tolbutamide on beta cell metabolism using NMR spectroscopy. FEBS J. 273: 5160-5168; 2006. Parker, J.C., Lavery, K.S., Irwin, N., Green, B.D., Greer, B., Harriott, P., O’Harte, F.P.M., Gault, V.A. and Flatt, P.R. Effects of daily treatment with naturally-occuring N-terminally truncated metabolites of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), GIP(3-42) and GLP-1(9-36), on insulin secretion and glucose homeostasis in ob/ob mice. J. Endocrinol., 191: 93-100; 2006. Hannan, J.M.A., Marenah, L., Ali, L., Rokeya, B., Flatt, P.R. and Abdel-Wahab, Y. Insulin secretory actions of extracts of Asparagus racemosus root in perfused pancreas, isolated islets and clonal pancreatic beta cells. J. Endocrinol. 192: 159-168; 2007 Hannan, J.M.A., Ali, L., Rokeya, B., Khaleque, J., Akhter M., Flatt, P.R. and Abdel-Wahab, Y. Soluble dietary fibre fraction of Trigonella foenum-graecum (fenugreek) seed improves glucose homeostasis in type 1 and type 2 diabetes by delaying carbohydrate digestion, absorption and enhancing insulin action. Br. J. Nutr. 97: 514-521; 2007. Patterson, S., Flatt, P.R. and McClenaghan, N.H. Homocysteine-induced impairment of pancreatic beta-cell responsiveness to a range of physiological and pharmacological insulin secretogoues is not reversed by catalase. Pancreas 34: 144-151; 2007. Parker, J.C., Irwin, N., Lavery, K.S., Green, B.D. O’Harte, F.P.M., Gault, V.A. and Flatt, P.R. Metabolic effects of sub-chronic ablation of the incretin receptors by daily administration of (Pro)3GIP and exendin(-9-39)amide in obese diabetic ob/ob mice. Biol. Chem. 388: 221-226; 2007. Gault, .VA., Hunter, K., Irwin, N., Greer, B., Harriott, P., O’Harte, F.P.M. andFlatt, P.R. Characterisation and glucoregulatory actions of a novel acylated form of the (Pro3)GIP receptor antagonist in type 2 diabetes. Biol. Chem. 388: 173-179; 2007 Irwin, N., McClean, P.L., Harriot, P. and Flatt, P.R. Beneficial effects of sub-chronic activation of glucagon-like peptide-1 (GLP-1) receptors on deterioration of glucose homeostasis and insulin secretion in aging mice. Exp. Gerontology 42: 296-300; 2007. Gault, V.A., McClean, P.L., Irwin, N., Power, G.J., McCluskey, J.T. and Flatt, P.R. Effects of sub-chronic treatment with the long-acting GIP receptor agonist, N-AcGIP, on glucose homeostasis in streptozotocin-induced diabetes. Pancreas 35: 73-79; 2007. McClean, P.L., Gault, V.A., Irwin, N., McCluskey, J.T. and Flatt, P.R. Daily administration of the GIP-R antagonist, (Pro)3GIP in streptozotocin induced diabetes suggests insulin-dependent mechanisms are critical to the anti-obesity-diabetes actions of (Pro)3GIP. Diabetes Obes. Metab. 10: 336-342; 2008 Green, B.D., Irwin, N. and Flatt, P.R. Direct and indirect effects of obestatin peptides on food intake and the regulation of glucose homeostasis and insulin secretion in mice. Peptides 28: 981-987; 2007. Irwin, N., McClean, P.L., Cassidy, R.C., O’Harte, F.P.M., Green, B.D., Gault, V.A., Harriott, P. and Flatt, P.R. Comparison of the antidiabetic effects of GIP- and GLP-1-receptor activation in obese diabetic (ob/ob) mice: Studies with DPP IV resistant N-AcGIP and exendin(1-39)amide. Diabetes Metab. Res Rev. 23: 572-579; 2007. Irwin, N., McClean ,P.L. and Flatt, P.R. Comparison of the sub-chronic antidiabetic effects of DPP IV resistant GIP and GLP-1 analogues in obese diabetic (ob/ob) mice. J. Pept. Sci. 13: 400-405; 2007. Gault, V.A., Hunter, K., Irwin, N., Green, B.D., Greer, B., Harriott, P., O’Harte, F.P.M. and, Flatt, P.R. Characterisation and biological activity of Glu3 amino acid substituted GIP receptor antagonists. Arch. Biochem. Biophys. 461: 263-274; 2007. O’Harte, F.P.M., Hunter, K., Gault, V.A., Irwin, N., Green, B.D., Greer, B., Harriott, P., Bailey, C.J. and Flatt, P.R. Antagonistic effects of two novel GIP analogues, (Hyp3)GIP and (Hyp3)GIPLys16PAL on the biological actions of GIP and longer term effects in diabetic ob/ob mice. Am. J. Physiol. 292: E1674-E1682; 2007. Gault ,V.A., McClean, P.L., Cassidy, R.C., Irwin, N. and Flatt, P.R.
Chemical GIP receptor antagonism protects against obesity, insulin resistance, glucose
intolerance and associated disturbances in mice fed high fat and cafeteria diets.
Diabetologia 50: 1752-1762; 2007.

Irwin, N., McClean, P.L., O’Harte, F.P.M., Gault, V.A., Harriott, P. and Flatt, P.R.
Early administration of the glucose-dependent insulinotropic polypeptide receptor antagonist,
(Pro3)GIP, prevents the development of diabetes and related metabolic abnormalities
associated with genetically-inherited obesity in ob/ob mice.
Diabetologia 50: 1532-1540; 2007.
Patterson, S., Flatt, P.R. and McClenaghan, N.H.
Major metabolic homocysteine-derivative, homocysteine thiolactone, exerts changes in
pancreatic beta-cell glucose-sensing, cellular signal transduction and integrity.
Arch. Biochem. Biophys. 461: 287-293; 2007.
Patterson, S., Scullion, S.M., McCluskey, J.T., Flatt, P.R. and McClenaghan, N.H.
Prolonged exposure to homocysteine results in diminished but reversible pancreatic beta-cell
responsiveness to insulinotropic agents.
Diabetes Metab. Res. Rev. 23: 324-334; 2006.
Kiely, A., McClenaghan, N.H., Flatt, P.R. and Newsholme, P.
Pro-inflammatory cytokines increase glucose, alanine and triacylglycerol utilization but
inhibit insulin secretion in a clonal pancreatic beta-cell line.
J. Endocrinol., 195: 113-123; 2007.
Abdel-Wahab, Y.H.A., Marenah,L., Flatt, P.R. and Conlon, J.M.
Insulin-releasing properties of the temporin family of antimicrobial peptides.
Protein Pept. Letts. 14: 702-707; 2007.
McKillop, A.M., Duffy, N.A., Lindsay, J.R., O’Harte, F.P.M., Bell, P. and Flatt, P.R.
Decreased dipeptidyl peptidase IV activity and GLP-1 degradation in type 2 diabetic
subjects.
Diabetes Clin.Res.Pract. 79: 79-85; 2008.
Duffy, N.A., Green, B.D., Irwin, N., Gault, V.A., McKillop, A.M., O’Harte, F.P.M. and
Flatt, P.R.
Effects of antidiabetic drugs on dipeptidyl peptidase IV activity: Nateglinide is an inhibitor
of DPP IV and augments the antidiabetic activity of glucagon-like peptide-1.
Eur J. Pharmacol. 568: 278-286; 2007.
McClean, P.L., Irwin, N., Cassidy, R.S., Holst, J.J., Gault, V.A. and Flatt, P.R.
GIP receptor antagonism using (Pro3)GIP reverses obesity, insulin resistance and associated
metabolic disturbances induced in mice by prolonged consumption of high fat diet.
Am. J. Physiol., 293: E1746-1755; 2007.
Cassidy, R.S., Irwin, N. and Flatt, P.R.
Effects of gastric inhibitory polypeptide (GIP) and related analogues on glucagon release at
normo- and hyperglycaemia in Wistar rats and isolated islets.
Biol. Chem. 389: 189-193; 2008.
Irwin, N., Hunter, K. and Flatt, P.R. Comparison of the sub-chronic metabolic effects of GIP receptor antagonism and PYY(3-36) receptor activation in high fat fed mice. Peptides 28: 2192-2198; 2007. Liu, H.K., McCluskey, J.T., McClenaghan, N.H. and Flatt, P.R. Streptozotocin-resistant BRIN-BD11 cells possess wide spectrum of toxin tolerance and enhanced insulin-secretory capacity. Endocrine 32: 20-29; 2007. Liu, H.K., McCluskey, J.T., McClenaghan, N.H. and Flatt, P.R. Interative exposure of clonal BRIN-BD11 cells to ninhydrin enables selection of robust toxin-resistant pancreatic beta cells but with decreased gene expression and insulin-secretory function. Pancreas 36: 294-301; 2008. Irwin, N., Hunter, K., Frizzell, N. and Flatt, P.R. Antidiabetic effects of sub-chronic administration of the cannabinoid receptor (CB1) antagonist, AM251, in obese diabetic (ob/ob) mice. Eur. J. Pharmacol. 581: 226-233; 2008. Irwin, N., Hunter, K. and Flatt, P.R. Comparison of independent and combined metabolic effects of GIP and CB1 receptor blockade in high-fat fed mice. Peptides 29: 1036-1041; 2008. Abdel-Wahab, Y.H.A., Power, G.J., Ng, M.T., Flatt, P.R. and Conlon, M.J. Insulin-releasing properties of the frog skin peptide pseudin-2 and its [Lys18]-substituted analogue. Biol. Chem. 389: 143-148; 2008. Flatt, P.R., Bailey, C.J and Green B.D. Dipeptidyl peptidase IV (DPPIV) and related molecules in type 2 diabetes. Front. Biosci. 13: 3648-3660; 2008. Taylor, A., Irwin, N., McKillop, A.M., Flatt, P.R. and Gault, V.A. Sub-chronic administration of 11beta-HSD1 inhibitor, carbenoxolone, improves glucose tolerance and insulin insensitivity in mice with diet-induced obesity. Biol. Chem. 2008 Jan 29, Epub Gault, V.A., Kerr, B.D., Irwin, N. and Flatt, P.R. C-terminal mini-PEGylation of glucose-dependent insulinotropic polypeptide exhibits metabolic stability and improved glucose homeostasis in ietary-induced diabetes. Biochem. Pharmacol., Mar 26 2008, Epub Conlon, J.M., Power, G.J., Abdel-Wahab, Y.H.A., Flatt, P.R., Jiansheng, H., Coquet, L., Leprince, J., Jouenne, T. and Vaudry, H. A potent non-toxic insulin-releasing peptide isolated from an extract of the skin of the Asian frog, Hylarana guntheri (Anura: Ranidae). Diabetes Research Group
(Publications 2001-)
REFEREED CONFERENCE ABSTRACTS & SHORT PAPERS
Kelly, C.M.N., Duffy, N., Flatt, P.R. and O’Harte, F.P.M. Peripheral administration of cholecystokinin octapeptide and islet amyloid polypeptide inhibits food intake in mice. Proc. Nutr. Soc., 60: 10A; 2001. Dixon, G., McClenaghan, N.H., Flatt, P.R., Nolan, J. and Newsholme, P. Effects of type-I and type II and LADA patient sera on viability, nitric oxide production and alanine-induced insulin secretion from clonal BRIN-BD11 cells. Proceedings of IREN Workshop on Bioengineering of the Ideal Surrogate Cell for Diabetes Insulin-Replacement Therapy, Hannover, p. 22, 2001. McCluskey, J.T., Hamin, M., McClenaghan, N.H. and Flatt, P.R. Effects of commercially available tissue culture media on the function of clonal insulin-secreting cells. Proceedings of IREN Workshop on Bioengineering of the Ideal Surrogate Cell for Diabetes Insulin-Replacement Therapy, Hannover, p. 12, 2001. Miguel, J.C., Abdel-Wahab, Y.H.A., Mathias, P.C.F. and Flatt, P.R. Functional characterisation of muscarinic receptor subtypes expressed in insulin secreting BRIN-BD11 cells. Proceedings of IREN Workshop on Bioengineering of the Ideal Surrogate Cell for Diabetes Insulin-Replacement Therapy, Hannover, p. 36, 2001. McClenaghan, N.H., Ball, A.J. and Flatt, P.R. Prolonged tolbutamide exposure specifically desensitises sulphonylurea- but not imidazoline-induced insulin release. Proceedings of IREN Workshop on Bioengineering of the Ideal Surrogate Cell for Diabetes Insulin-Replacement Therapy, Hannover, p. 49, 2001. O’Harte, F.P.M., Kelly, C.M.N. and Flatt, P.R. Actions of cholecystokinin-8 and related analogues on insulin-secreting cells. Proceedings of IREN Workshop on Bioengineering of the Ideal Surrogate Cell for Diabetes Insulin-Replacement Therapy, Hannover, p. 50, 2001. Abdel-Wahab, Y.H.A., Marenah, L., Shaw, C. and Flatt, P.R. Isolation and characterisation of various insulin releasing peptides from skin secretions of Rana pipiens. Proceedings of IREN Workshop on Bioengineering of the Ideal Surrogate Cell for Diabetes Insulin-Replacement Therapy, Hannover, p. 52, 2001. McClenaghan, N.H., Ball, A.J. and Flatt, P.R. Nateglinide exhibits glucose-sensitive K-ATP dependent and independent insulinotropic actions. Diabetologia 44 (1): A215; 2001. McKillop, A.M., Mooney, M.H., O’Harte, F.P.M. and Flatt, P.R. Evaluation of glycated insulin in plasma and biological tissues of diabetic animal models. Diabetologia 44 (1): A318; 2001. Brennan, L., Shine, A., Hewage, C., Brindle, K.M., Malthouse, J.P.G., McClenaghan, N.M., Flatt, P.R. and Newsholme, P. A NMR study of glucose and alanine metabolism by the beta cell lines RINm5F and BRIN-BD11. Diabetologia 44 (1): A124; 2001. Flatt, P.R., Gault, V.A., Harriott, P. and O’Harte, F.P.M. Antagonist actions of novel (Pro3)GIP analogue and GIP(3-42) on cyclic AMP production and insulin secretion. Diabetologia 44 (1): A195; 2001. Gault, V.A., Harriott, P., Flatt, P.R. and O’Harte, F.P.M. GIP analogues substituted at Ala2 exhibit improved plasma stability and insulin-releasing activity. Diabetologia 44 (1): A195; 2001. O’Harte, F.P.M., Gault, V.A., Harriott, P., Parker, J.C. and Flatt, P.R. DPPIV resistant N-terminally modified GIP analogues with enhanced insulinotropic activity. Diabetologia 44 (1): A194; 2001. Abdel-Wahab, Y.H.A., Marenah, L., Shaw, C. and Flatt, P.R. Isolation and structural characterisation of insulinotropic peptides from Bombina variegata. Diabetologia 44 (1): A135; 2001. Mooney, M.H., Gault, V.A., Abdel-Wahab, Y.H.A., Flatt, P.R. and O’Harte, F.P.M. Identification of Tyr1-glucitol GIP in intestines of diabetic mice with enhanced insulin-releasing activity. Diabetologia 44 (1): A319; 2001. Abdel-Wahab, Y.H.A., Kelly, C.M.N., McLoughlin, L., Flatt, P.R. and O’Harte, F.P.M. Peripheral administration of cholecystokinin octapeptide and caerulin inhibits food intake in Swiss TO mice. Proc. Nutr. Soc., 60: 153A; 2001. Green, B.D., O’Harte, F.P.M., Harriott, P., Green, B. and Flatt, P.R. N-terminally modified GLP-1(7-36)amide is resistant to dipeptidyl peptidase-IV degradation whilst maintaining insulinotropic action. Proc. Nutr. Soc., 60: 154A; 2001. O’Harte, F.P.M., Kelly, C.M.N. and Flatt, P.R. Biological activity of cholecystokinin octapeptide and related analogoues on insulin secretion from pancreatic beta cells. Proc. Nutr. Soc., 60: 154A; 2001. Mooney, M.H., Abdel-Wahab, Y.H.A., Flatt, P.R. and O’Harte, F.P.M. Detection of glycated GLP-1 within the intestinal tissue of normal and diabetic animals. Proc. Nutr. Soc., 60: 153A; 2001. J.R.Lindsay, A.M. McKillop, M.H. Mooney, F.P.M. O’Harte, P.R.Flatt and P.M.Bell. Detection of glycated insulin in plasma of type 2 diabetic subjects using a novel radioimmunassay. Faculty of Medicine and Health Sciences Annual Research Workshop, Queens University of Belfast, p. 47, 2001 Lindsay, J.R., McKillop, A.M., Mooney, M.H., O’Harte, F.P.M., Flatt, P.R. and Bell, P.M. Detection of glycated insulin in plasma of type 2 diabetic subjects using a novel radioimmunoassay. Irish Journal of Medical Science 170 (Suppl 2): 10; 2001. McKillop, A.M., Meade, A., Flatt, P.R. and O’Harte, F.P.M. Structural characterisation of glycated proinsulin. Irish Journal of Medical Science 170 (Suppl 2): 11; 2001. O'Harte, F.P.M., Gault, V.A., Harriott, P., Parker, J.C. and Flatt, P.R. Stable amino-terminally modified analogues of glucose-dependent insulinotropic polypeptide with improved insulin releasing activity. Irish Journal of Medical Science 170 (Suppl 2): 10; 2001. Mooney, M.H., Gault, V.A., Flatt, P.R. and O'Harte, F.P.M. Detection of glycated glucose-dependent insulinotropic polypeptide in the intestines of diabetic mice and assessment of its biological activity in vitro. Irish Journal of Medical Science 170 (Suppl 2): 11; 2001. Au, S.T.B., Lindsay, J.R., Kelly, C.M., O'Harte, F.P.M., Flatt, P.R. and Bell, P.M. Amino terminal glycation of glucose-dependent insulinotrophic polypeptide prolongs its insulinotropic action in type 2 diabetes mellitus. Irish Journal of Medical Science 170 (Suppl 2): 28; 2001. Lindsay, J.R., Au, S.T.B., Kelly, C.M., O’Harte, F.P.M., Flatt, P.R. and Bell, P.M. Prolonged insulinotropic effect in type 2 diabetes of N-terminally glycated glucose-dependent insulinotropic polypeptide. 67th Meeting Ulster Society of Internal Medicine, p. 5, Belfast, 2001. McClenaghan, N.H. and Flatt, P.R. Diabetes Uncovered. Irish Scientist 10: 242; 2002. McKillop, A.M., Mooney, M.H., O’Harte, F.P.M. and Flatt, P.R. Secretion of glycated insulin from pancreatic beta-cells in animal models of diabetes. Diabetes Metab. 28: 3S106; 2002. Picton, S.F., McCluskey, J.T., Flatt, P.R. and McClenaghan, N.H. Effects of cytotoxic agents on functional integrity and antioxidant enzymes in clonal beta cells. Diabetes Metab. 28: 3S106; 2002. Lindsay, J.R., McKillop, A.M., Mooney, M.H., O’Harte, F.P.M., Bell, P.M. and Flatt, P.R. Elevated plasma glycated insulin in type 2 diabetes, detected using a novel radioimmunoassay. Diabetic Med. 19 (Suppl 1): 28; 2002. O’Harte, F.P.M., Green, B.D., Greer, B., Harriott, P. and Flatt, P.R. N-acetyl glucagon-like peptide-1 is resistant to dipeptidyl-peptidase i.v. and exhibits strong insulinotropic activity. Diabetic Med. 19 (Suppl 1): 14; 2002. Green, B.D., Flatt, P.R., Harriott, P. and O’Harte, F.P.M. Novel stable Val8-glucagon-like peptide-1 analogue with potent insulin releasing activity. Diabetic Med. 19 (Suppl 1): 80; 2002. Green, B.D., O’Harte, F.P.M., Greer, B., Harriott, P. and Flatt, P.R. Enhanced plasma stability, receptor binding, cyclic-AMP production and insulin-releasing activity of two novel penultimate N-terminally substituted analogues of glucagon-like peptide-1. Diabetologia 45 (Suppl. 2): A159; 2002. Gault, V.A., Green, B.D., Greer, B., Harriott, P., Flatt, P.R. and O’Harte, F.P.M. N-terminally modified analogues of glucose-dependent insulinotropic polypeptide exhibit improved insulinotropic activity and antihyperglycaemic potential compared with glucagon-like peptide-1 counterparts. Diabetologia 45 (Suppl. 2): A177; 2002. Flatt, P.R., Gault, V.A., Harriott, P., Greer, B., Mooney, M.H., Bailey, C.J. and Flatt, P.R. Novel N-Fmoc and N-palmitate analogues of glucose-dependent insulinotropic polypeptide exhibit DPP IV resistance, increased insulin-releasing activity and antidiabetic action. Diabetologia 45 (Suppl. 2): A177; 2002. Mooney, M.H., Gault, V.A., Flatt, P.R., Harriott, P., Greer, B., Bailey, C.J. and O’Harte, F.P.M. Antidiabetic potential of four novel analogues of glucose-dependent insulinotropic peptide demonstrated in an animal model of Type 2 diabetes. Diabetologia 45 (Suppl. 2): A178; 2002. O’Harte, F.P.M., Gault, V.A., Harriott, P., Green, B.D. and Flatt, P.R. Comparative studies with exendin(9-39)amide and the novel (Pro3)GIP receptor antagonist indicates that glucose-dependent insulinotropic polypeptide is the major hormone of the enteroinsular axis. Diabetologia 45 (Suppl. 2): A178; 2002. Abdel-Wahab, Y.H.A., Marenah, L., Shaw, C. and Flatt, P.R. Isolation and structural characterisation of novel insulinotropic peptides from the skin secretion of Rana Pipiens. Diabetologia 45 (Suppl. 2): A178; 2002. McKillop, A.M., Lindsay, J.R., Mooney, M.H., O’Harte, F.P.M., Bell, P.M. and Flatt, P.R. Electrospray ionization mass spectrometry characterization and measurement of circulating glycated insulin and responses to fasting and feeding in Type 2 diabetic subjects. Diabetologia 45 (Suppl. 2): A393; 2002. O’Harte, F.P.M., McLoughlin, L.P.M., Kelly, C.M.N., and Flatt, P.R. Peripheral GLP-1 receptors are involved in regulating voluntary food intake in mice. Irish Neurosciences Meeting, Tullamore, p32-33, 2002. Lindsay, J.R., Au, S.T.B., Kelly, C.M., O’Harte, F.P.M., Flatt, P.R. and Bell, P.M. A novel amino-terminally glycated analogue of glucose-dependent insulinotropic polypeptide (GIP) with prolonged insulinotropic activity in type 2 diabetes mellitus. Diabetes 51 (Suppl. 2): A341; 2002. Sweeney, C.J., Ball, A.J., Flatt, P.R. and McClenaghan, N.H. Prolonged exposure of clonal pancreatic beta cells to sulphonylureas specifically desensitises drug, but not nutrient-induced insulin release. Proceedings of the Royal Academy of Medicine in Ireland Biomedical Sciences Section, Belfast, p. 21, 2002. Lindsay, J.R., McKillop, A.M., Mooney, M.H., O’Harte, F.P.M., Flatt, P.R. and Bell, P.M. Demonstration of diurnal variation of plasma glycated insulin in type 2 diabetes. Endocrine Abst., 3: P85; 2002. Picton, S.F., Flatt, P.R. and McClenaghan, N.H. Differential acute and long-term actions of nutrient ester exposure on clonal pancreatic beta cells. Proceedings of the Royal Academy of Medicine in Ireland Biomedical Sciences Section, Belfast, p. 23, 2002. Mooney, M.H., Gault, V.A., Flatt, P.R., Harriott, P. and O’Harte, F.P.M. N-terminally modified degradation resistant analogues of glucose-dependent insulinotropic polypeptide display enhanced antidiabetic action. Irish Journal of Medical Science 171 (Suppl. 3): 9; 2002. O’Harte, F.P.M., Gault, V.A., Harriott, P., Green, B.D. and Flatt, P.R. Receptor antagonist studies indicate that GIP is a more important enteroinsular axis hormone than GLP-1 in obese diabetic (ob/ob) mice. Irish Journal of Medical Science, 171 (Suppl. 3): 18; 2002. Lindsay, J.R., Duffy, N., McKillop, A.M., Ardill, J., O’Harte, F.P.M., Flatt, P.R. and Bell, P.M. Metformin inhibits dipeptidyl peptidase IV (DPP IV) activity in type 2 diabetes. Irish Journal of Medical Science, 171 (Suppl. 3): 29; 2002. McKillop, A.M., Lindsay, J.R., Mooney, M.H., Flatt, P.R., Bell, P.M. and O’Harte, F.P.M. Detection, isolation and fluctuation of glycated insulin in type 2 diabetic subjects. Irish Journal of Medical Science, 171 (Suppl. 3): 31; 2002. Lindsay, J.R., McKillop, A.M., Mooney, M.H., O’Harte, F.P.M., Flatt, P.R. and Bell, P.M. Nateglinide effects on te secretion of glycated insulin and glucose tolerance in subjects with Type 2 diabetes. Endocrine Abst., 4: P32; 2002. McKillop, A.M., Duffy, N., Lindsay, J.R., O’Harte, F.P.M., Bell, P.M. and Flatt, P.R. Decreased activity of dipeptidyl peptidase-IV potentially enhances glucagon-like peptide-1 (7-36)amide and gastric inhibitory polypeptide stability in Type 2 diabetics. Diabetic Med. 20 (Suppl. 2): 37; 2003. Abdel-Wahab, Y.H.A., Marenah, L., Shaw, C. and Flatt, P.R. Isolation and structural characterisation of novel insulinotropic peptides from the skin secretions of Rana palustris. Diabetic Med. 20 (Suppl. 2): 35; 2003. Green, B.D., Gault, V.A., Harriott, P., Greer, B., Mooney, M.H., Flatt, P.R. and O’Harte, F.P.M. Stability, cAMP production and antihyperglycaemic activity of Pro3-substituted analogues of GLP-1 and GIP. Diabetic Med. 20 (Suppl. 2): 36; 2003. Mooney, M.H., Gault, V.A., Harriott, P., Flatt, P.R. and O’Harte, F.P.M. Fragment peptides reveal bioactive domains critical for insulin-releasing activity of glucose-dependent insulinotropic polypeptide. Diabetic Med. 20 (Suppl. 2): 35; 2003. McCluskey, J.T., Meade, A.M., McClenaghan, N.H. and Flatt, P.R. Specificity, time-dependency and reversibility of hyperglycaemia-induced beta-cell dysfunction. Diabetic Med., 20 (Suppl. 2): 34; 2003. Duffy, N.A., McLoughlin L.P.M., Kelly, C.M.N., Flatt, P.R. and O’Harte, F.P.M. DPPIV inhibition by metformin potentiates the satiating effect of glucagon-like peptide-1 (GLP-1) in mice. Diabetic Med. 20 (Suppl. 2): 36-37; 2003. McClenaghan, N.H., Ball, A.J., McCluskey, J.T. and Flatt, P.R. K-ATP channel-dependent and –independent insulinotropic actions of nateglinide are enhanced by gut peptides, glucagon-like peptide-1 (7-36) amide and gastric inhibitory polypeptide. Diabetic Med. 20 (Suppl. 2): 36; 2003. O’Harte, F.P.M., Gault, V.A., Harriott, P., Irwin, N., Mooney, M.H. and Flatt, P.R. Biological activity of two novel N-terminal Ala2-substituted analogogues of glucose-dependent insulinotropic polypeptide (GIP). Diabetic Med. 20 (Suppl. 2): 35-36; 2003.
Gault, V.A., Parker, J.C., Harriott, P., Mooney, M.H., Flatt, P.R. and O’Harte, F.P.M.
Major metabolite of glucose-dependent insulinotropic polypeptide (GIP), GIP(3-42), acts as a
GIP receptor antagonist in vivo.
Diabetic Med. 20 (Suppl. 2): 36; 2003.
Lindsay, J.R., Duffy, N., McKillop, A.M., Ardill, J., O’Harte, F.P.M., Flatt, P.R. and Bell,
P.M.
Inhibition of dipeptidyl peptidase IV (DPP IV) activity by oral metformin in Type 2 diabetes.
Diabetic Med. 20 (Suppl. 2): 4-5; 2003.
O’Harte, F.P.M., Duffy, N.A., Kelly, C.M.N. and Flatt, P.R.
Regultion of voluntary food intake in mice is affected by glucagon-like peptide-1 receptor
mediated mechanisms.
In: Proceedings of International Meeting on Digestive Hormones, Appetite and Energy
Balance, London, p, 36, 2003.
Duffy N.A., McLoughlin L.P.M., Kelly C.M.N, Flatt P.R. and O’Harte F.P.M.
Metformin combined with glucagons-like peptide-1 reduces food intake in mice
by inhibition of dipeptidyl peptidase IV activity.
Proceedings of Inaugural BioNet Conference, Galway, p. 29, 2003.

Irwin N., Gault, V.A., Flatt, P.R., Mooney, M.H. and O’Harte, F.P.M.
Biological activity of mono- and di-substituted analogues of gastric inhibitory polypeptide
(GIP).
Proceedings of Inaugural BioNet Conference, Galway, p. 28, 2003.
Irwin, N., Green, B.D., Liu, H-K., McCluskey, J.T., McClenaghan, N.H., Gault, V.A.,
Harriott, P., Greer, B., O’Harte, F.P.M. and Flatt, P.R.
DPP IV resistant GLP-1 analogue N-acetyl-GLP-1 has improved effects on pancreatic beta-
cell associated gene expression.
Irish Journal of Medical Science 172 (Suppl. 1): 24-25; 2003.
O’Harte, F.P.M., Green, B.D., Mooney, M.H, Gault, V.A., Irwin, N., Harriott, P., Greer, B.
and Flatt, P.R.
Comparison of the activity of the novel dipeptidylpeptidase IV resistant GLP-1 receptor
antagonist (Lys9)GLP-1 with GLP-1(9-36)amide and exendin-4(9-39).
Irish Journal of Medical Science 172 (Suppl. 1): 10-11; 2003.
Green, B.D., Gault, V.A., Mooney, M.H., Irwin, N., Harriott, P., Greer, B., O’Harte, F.P.M.
and Flatt, P.R.
DPP IV degradation, receptor binding, insulin secreting and antihyperglycaemic
characteristics of palmitate-dervitised GLP-1 analogues.
Irish Journal of Medical Science 172 (Suppl. 1): 41; 2003.
McCluskey, J.T., Liu, H-K., Green, B.D., McClenaghan, N.H. and Flatt, P.R.
The beneficial effects on insulin secretion and function of beta cells following long-term
culture with ultratrace elements: vanadate, tungstate and molybdate.
Irish Journal of Medical Science 172 (Suppl. 1): 40-41; 2003.
Green, B.D., Gault, V.A., Mooney, M.H., Irwin, N., Harriott, P., Greer, B., O’Harte, F.P.M. and Flatt, P.R. Molecular, cellular and biological characteristics of DPP IV-resistant acetylated analogues of GLP-1. Diabetic Med 21 (Suppl. 2): 26; 2004. Gault, V.A., Green B.D., Irwin, N., Harriott, P., Greer, B., Flatt, P.R. and O’Harte, F.P.M. Development and characterisation of novel N-terminal Glu9-substituted agonists of glucagon-like peptide-1 (GLP-1). Diabetic Med. 21 (Suppl. 2): 26; 2004. O’Harte, F.P.M., Green, B.D., Gault, V.A., Irwin, N., Mooney, M.H., Harriott, P., Greer, B. and Flatt, P.R. (Lys9)GLP-1 lacks insulinotropic activity but acts as a potent novel GLP-1 receptor antagonist in vivo. Diabetic Med. 21 (Suppl. 2): 43; 2004. McKillop, A.M., Lindsay, J.R., O’Harte, F.P.M., Bell, P.M. & Flatt, P.R. Meal and glucose-dependent polypeptide regulation of circulating glycated insulin in type 2 diabetic subjects. Diabetic Med. 21 (Suppl. 2): 6; 2004. Picton, S.F., Luther, M., Marenah, L., Naujok, O., Jorns, A., Jones, P., Flatt, P.R., Lenzen, S. & Bailey, C.J. Differentiation of mouse embryoinc stem cells into insulin-producing cells. Diabetic Med. 21 (Suppl. 2): 19; 2004. McClenaghan, N.H., Ball, A.J., McCluskey, J.T. & Flatt, P.R. Chonic exposure to sulphonylureas impairs insulin secretion without altering expression of K-ATP channel components. Diabetic Med. 21 (Suppl. 2): 27; 2004. Abdel-Wahab, Y.H.A., Marenah, L., Orr, D.F., Shaw, C. & Flatt, P.R. Isolation and characterisation of a novel class of insulinotropic peptides in the skin of the frog Agalychnis litodryas. Diabetic Med. 21 (Suppl. 2): 42; 2004. Marenah, L., Orr, D.F., Flatt, P.R., McClean, S., Shaw, C. & Abdel-Wahab, Y.H.A. Esculentin-1B and brevinins-1E and 2EC are novel insulin releasing peptides in skin secretions of Rana saharica frogs. Diabetic Med. 21 (Suppl. 2): 42; 2004. Green, B.D., Irwin, N., Gault, V.A., O'Harte, F.P.M., Bailey, C.J. and Flatt, P.R. Chronic treatment of obese hyperglycaemic ob/ob mice with exendin(9-39)amide suggests a minor role for endogenous GLP-1 in metabolic abnormalities of obesity-diabetes. Diabetologia 47 (Suppl. 1): A239; 2004. Flatt, P.R., Irwin, N., Green, B.D., Harriott, P., Gault, V.A. and O'Harte, F.P.M. Daily administration of GIP receptor antagonist alleviates glucose intolerance and counters insulin resistance in an animal model of obesity and type 2 diabetes. Diabetologia 47 (Suppl. 1): A282; 2004. Irwin, N., Gault, V.A., Green, B.D., Harriott, P., O'Harte, F.P.M. and Flatt, P.R. Long-acting Tyr1-modified analogues of GIP with significantly improved antihyperglycaemic and insulinotropic properties. Diabetologia 47 (Suppl. 1): A43; 2004. Abdel-Wahab, Y.H.A., Marenah, L., Orr, D.F., Shaw, C. and Flatt, P.R. Isolation and structural characterisation of a novel 13 amino acid insulin-releasing peptide from the skin secretion of Agalychnis calcalifer. Diabetologia 47 (Suppl. 1): A6; 2004. McClenaghan, N.H., McCluskey, J.T., Flatt, P.R. and Patterson, S. Homocysteine, a metabolic syndrome risk factor, exerts detrimental effects on insulin secretion and pancreatic beta cell function. Diabetologia 47 (Suppl. 1): A171-172; 2004. McKillop, A.M., Duffy, N., Lindsay, J.R., Flatt, P.R., Bell, P. and O’Harte, F.P.M. Decreased dipeptidyl peptidase IV activity and degradation of glucagon-like peptide-1(7-36)amide in type 2 diabetes. Diabetologia 47 (Suppl. 1): A286; 2004. McCluskey J.T., Irwin N., Gault, V.A., Green, B.D., Flatt, P.R. and O'Harte, F.P.M. Longer-term ablation of GIP signalling in normal mice demonstrates importance of GIP for glucose homeostatis as part of the enteroinsular axis. In: Proceedings of the EASD Study Group Meeting on Molecular Aspects of Pancreatic Islet Function, Prien Germany, p. 26, 2004. McClenaghan, N.H., Ball, A.J., McCluskey, J.T. and Flatt, P.R. Insulin secretory dysfunction induced by chronic sulphonylurea exposure does not involve alteration of K-ATP channel expression. In: Proceedings of the EASD Study Group Meeting on Molecular Aspects of Pancreatic Islet Function, Prien Germany, p. 29, 2004. Marenah, L., McCluskey, J.T., Abdel-Wahab, Y.H.A., McClenaghan, N.H., Picton, S., Bailey, C.J., Naujok, O., Lenzen, L. and Flatt, P.R. Defferentiation of mouse embryonic stem cells into cells expressing specific islet genes and hormones. In: Proceedings of the EASD Study Group Meeting on Molecular Aspects of Pancreatic Islet Function, Prien Germany, p. 40, 2004. Keane, D., Dixon, G., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. Palmitic acid modulates clonal pancreatic beta cell nutrient metabolism, insulin secretion, gene expression and functional integrity. In: Proceedings of the EASD Study Group Meeting on Molecular Aspects of Pancreatic Islet Function, Prien Germany, p. 9, 2004. O’Harte, F.P.M., Irwin, N., Gault, V.A., Green, B.D. and Flatt, P.R. Assessment of the antidiabetic potential of two fatty acid derivatized GIP analogues. Regul Pept 122: 33-34; 2004. O’Harte, F.P.M., Hunter, K., Irwin, N., Green, B.D., Flatt, P.R. and Gault, V.A. Two novel fatty acid modified GIP analogues with improved antidiabetic potential. Proceedings 2nd BioNet Conference, Carlow, Ireland, p.54, 2004. Lavery, K.S., Parker, J.C., Green, B.D., Irwin, N., Gault, V.A., Flatt, P.R. and O’Harte, F.P.M. The truncated incretin hormone glucagon-like peptide-1(9-36)amide has a significant effect on glucose disposal in vitro and in vivo. Proceedings 2nd BioNet Conference, Carlow, Ireland, p.21, 2004. Alana, I., Hewage C.M., Malthouse J.P.G., Parker J., Gault, V.A. and O’Harte, F.P.M. NMR and modeling studies of glucose-dependent insulinotropic polypeptide. 17th FENC/32nd Ampere, Lille France, 2004. Picton, S., Bailey, C.J., Abdel-Wahab, Y.H.A. and Flatt, P.R. Immunosuppressant drugs and pancreatic beta cell function. In: Proceedings of the 1st TONECA Conference on the Aetiology, Pathology and Prediction of Type 1 Diabetes in Europe, Hannover, p. 17, 2004. Abdel-Wahab, Y.H.A., McClenaghan, N.H., Picton, S.F., McCluskey, J.T. and Flatt, P.R. Effects of T1DM cytotoxic damage on functional integrity and antioxidand enzymes in clonal beta cells. In: Proceedings of the 1st TONECA Conference on the Aetiology, Pathology and Prediction of Type 1 Diabetes in Europe, Hannover, p. 18, 2004. Cunningham, G., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. Cytokines and nutrients regulate metabolism, gene expression and functional integrity of pancreatic beta cells. In: Proceedings of the 1st TONECA Conference on the Aetiology, Pathology and Prediction of Type 1 Diabetes in Europe, Hannover, p. 18, 2004. Gault, V.A., Irwin, N., O’Harte, F.P.M., Green, B.D. and Flatt, P.R. Antidiabetic potential of a long-acting derivative of GIP following once daily administration in type 2 diabetes. Regul Pept 122: 20; 2004. O’Harte, F.P.M., Irwin, N., Gault, V.A., Green, B.D. and Flatt, P.R. C-16 fatty acid derivatised GIP analogues as potential agents for diabetes therapy. Irish J. Med. Sci. 173 (Suppl. 1): 10; 2004. Hunter, K., Irwin, I., Green, B.D., Flatt, P.R., O’Harte, F.P.M. and Gault, V.A. Novel long-ating enzyme resistant glucose-dependent insulinotropic polypeptide receptor agonists with improved antihyperglycaemic and insulinotropic activity. Irish J. Med. Sci. 173 (Suppl. 1): 35-36; 2004. Green, B.D., Liu, H.K., McClenaghan, N.H., McCluskey, J.T. and Flatt, P.R. Beneficial effects of long-term treatment of pancreatic beta-cells with ultratrace elements vanadate, tungstate and molybdate. In: Proceedings of the 12th International Symposium on Trace Elements in Man and Animals, Coleraine, p. 96, 2005. McClenaghan, N.H., McCluskey, J.T., Flatt, P.R. & Patterson, S. Acute exposure to the metabolic syndrome risk factor, homocysteine, exerts detrimental insulinotropic and pancreatic beta cell actions. Diab. Med 22 (Suppl. 2): 1-2; 2005. Cromwell, D., Flatt, P.R. & McClenaghan, N.H. Differential acute and chronic insulinotropic pancreatic beta-cell actions of mixtures of amino acids are modulated by diverse classes of metabolic nutrient esters. Diab. Med 22 (Suppl. 2): 2; 2005. Lavery, K.S., Parker, J.C., Irwin, N., Gault, V.A., Flatt, P.R., Green, B.D. & O’Harte, F.P.M. The truncated peptide glucagons-like peptide-1(9-36)amide has no insulin-releasing activity but retains a significant effect on glucose disposal in vitro and in vivo. Diab. Med 22 (Suppl. 2): 17; 2005. Picton, S.F., Naujok, O., Jorns, A., Luther, M., Marenah, L., Kamagate, A., Herchuelz, A., Lenzen, S., Flatt, P.R., Jones, P. & Bailey, C.J. Implantation of pseudoisletes developed from embryonic stem cells. Diab. Med 22 (Suppl. 2): 33; 2005. Patterson, S., McCluskey, J.T., Flatt, P.R. and McClenaghan, N.H. Impaired insulin secretion and pancreatic beta cell dysfunction induced by homocysteine. In: Proceedings of the 2nd TONECA Conference on the Aetiology, Pathology and Prediction of Type 1 Diabetes in Europe, Brighton, p. 27, 2005. Abdel-Wahab, Y.H.A., Liu, H.K., McCluskey, J.T., McClenaghan, N.H. and Flatt, P.R. Generation and characterisation of toxin-resistant clonal insulin-secreting cells. In: Proceedings of the 2nd TONECA Conference on the Aetiology, Pathology and Prediction of Type 1 Diabetes in Europe, Brighton, p. 23, 2005. Hannan, J.M.A., Abdel-Wahab, Y.H.A., Marenah, L., Khaleque, J., Akhter, M., Ali, L. and Flatt, P.R. Mechanism of insulin secretory effects of traditional antidiabetic plant extract PE027. Diabetologia 48 (Suppl 1): A276-A277; 2005. Brennan, L., Hewage, C., Malthouse, J., McClenaghan, N.H., Flatt, P.R. and Newsholme, P. Effects of antidiabetic drugs on beta cell glucose metabolism in a clonal cell line, BRIN-BD11. Diabetologia 48 (Suppl 1): A163; 2005. Flatt, P.R. Design and actions of improved glucagon-like peptide-1 (GLP-1) for diabetes therapy. In: Proceedings of the Meeting of the Irish Area Section of the Biochemical Society, Maynooth, Ireland, p.3, 2005. O’Harte, F.P.M., Irwin, N., Green, B.D., Gault, V.A. and Flatt, P.R. Daily treatment with the novel GIP receptor antagonist (Pro3)GIP, improves glucose tolerance and reduces insulin resistance in an animal model of obesity and type 2 diabetes. Proceedings 3rd BioNet Conference, Tallaght, Ireland. (in press). O’Harte, F.P.M., Irwin, N., Green, B.D., Harriott, P., Greer, B., Gault, V.A. and Flatt, P.R. Once daily administration of (Pro3)GIP ameliorates glucose intolerance and improves insulin sensitivity in obese diabetic (ob/ob) mice. Irish Journal of Medical Science, (in press). O’Harte, F.P.M., Irwin, N., Green, B.D., Gault, V.A., Cassidy, R.S., Harriott, P. and Flatt, P.R. Effects of long-term activation of glucose-dependent insulinotropic polypeptide receptor on glucose tolerance and insulin secretion in normal mice. Diabetic Med. 23 (Suppl 2): 22; 2006 Gault, V.A., Irwin, N., Green, B.D., O’Harte, F.P.M. and Flatt, P.R. Long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor agonist restores beta-cell glucose responsiveness in ageing mice. Diabetic Med. 23 (Suppl 2): 31; 2006 Hill, A.J., Marshall, A.H., McCance, D.R. and Flatt, P.R. Dietary intake and habits of pregnant women with diabetes. Diabetic Med. 23 (Suppl 2): 99; 2006 Abdel-Wahab, Y.H.A., Liu, H.K., McClenaghan, N.H. and Flatt, P.R. Generation of toxin-resistant clonal insulin-secreting cells for study of mechanisms underlying beta cell damage and repair. Diabetic Med. 23 (Suppl 2): 33-34; 2006 Irwin, N., Gault, V.A., Green, B.D., Greer, B., Harriott, P., Bailey, C.J., O’Harte, F.P.M. and Flatt, P.R. Novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide (GIP) with enhanced antihyperglycaemic and insulinotropic properties. Diabetic Med. 23 (Suppl 2): 8; 2006. Flatt, P.R., Irwin, N., McClean, P.L., Green, B.D., Bailey, C.J., Gault, V.A. and O’Harte, F.P.M. Early administration of the GIP receptor antagonist (Pro3)GIP counters development of hyperglycaemia, glucose intolerance and insulin resistance in genetic obesity. Diabetologia 49 (Suppl 1): 108-109; 2006. Irwin, N., Clarke, G.C., Gault, V.A., Green, B.D., Harriott, P., O’Harte, F.P.M. and Flatt, P.R. Long-acting analogues of GIP with significantly improved antihyperglycaemic and insulinotropic properties: N-terminal modification versus mid-cahain acylation. Diabetologia 49 (Suppl 1): 109-110; 2006. McKillop, A.M., Duffy, N.A., Lindsay, J.R.,Green, B.D., O’Harte, F.P.M., Bell, P.M. and Flatt, P.R. Insulinotropic actions of nateglinide are accompanied by inhibition of dipeptidyl peptidase-IV activity. Diabetologia 49 (Suppl 1): 482-483; 2006. O’Harte, F.P.M., Hunter, K., Gault, V.A., Irwin, N., Harriott, P and Flatt, P.R. Cellular and metabolic evaluation of (hydroxyproline3)-GIP as a new stable receptor antagonist with antidiabetic potential. Diabetologia 49 (Suppl 1): 401-402; 2006. Gault, V.A., Hunter, K., Irwin, N., Green, B.D., O’Harte, F.P.M. and Flatt, P.R. Characterisation of novel glucose-dependent insulinotropic polypeptide (GIP) antagonists generated through amino acid substitution at position Glu3. Diabetologia 49 (Suppl 1): 408-409; 2006. O’Harte F.P.M., Hunter K., Gault V.A., Irwin N., Harriott P. and Flatt P.R. Evaluation of the antidiabetic potential of (Hyp3)GIP a new GIP receptor antagonist. Irish J. Med. Sci. 175 (Suppl. 2): p31; 2006. Irwin, N., Parker, J.C., Gault, V.A., Greer, B., Harriott, P., O’Harte, F.P.M. and Flatt, P.R. N-terminally truncated metabolite of glucose-dependent insulinotropic polypeptide (GIP) but not glucagon-like peptide-1 (GLP-1) improves glucose homeostasis in ob/ob mice through alleviation of insulin resistance. Diabetic Med. 24 (Suppl 1): 22; 2007. O’Harte, F.P.M., Irwin, N., Gault, V.A., McClean, P.L., Cassidy, R.S., Harriott, P. and Flatt, P.R. Antidiabetic effects of sub-chronic administration of stable incretin mimetics N-AcGIP and exendin-4 (1-39)amide in obese-diabetic mice. Diabetic Med. 24 (Suppl 1): 22; 2007. Paget, M.B., Murray, H.E., Bailey, C.J., Flatt, P.R. and Downing, R. Insulin secretion from BRIN-BD11 cells in response to co-culture with endothelial cells and a thiazolidenedione. Diabetic Med. 24 (Suppl 1): 32-33; 2007. Abdel-Wahab, Y.H.A., Mathews, J.N. and Flatt,P.R. Momordica charantia (karela) aqueous seed extract stimulates insulin secretion and insulin action in vitro. Diabetic Med. 24 (Suppl 1): 33; 2007. Gault, V.A., McClean, P.L., Irwin, N., McCluskey, J.T. and Flatt, P.R. Effects of GIP-receptor antagonism in a streptozotocin-induced model of insulin deficiency. Diabetic Med. 24 (Suppl 1): 40; 2007. McClean, P.L., Gault, V.A., Irwin, N., Power, G.J., McCluskey, J.T. and Flatt, P.R. Effects of daily administration of the glucose-dependent insulinotropic polypeptide (GIP) agonist, N-acetyl-GIP, in streptozotocin-induced diabetic mice. Diabetic Med. 24 (Suppl 1): 40; 2007. Green, B.D., Irwin, N. and Flatt, P.R. Direct and indirect effects of the anorectic hormone obestatin on glucose regulation and insulin secretion in mice. Diabetic Med. 24 (Suppl 1): 41; 2007. Brennan, L., Scullion, S.M., Mion, B., Hewage, C. Malthouse, J.P., Flatt, P.R., Newsholme, P. and McClenaghan, N.H. 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Source: http://www.diabetes.ulster.ac.uk/IMG/pdf/DRG_Pubs_0608.pdf