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Berberine for Diabetes Mellitus Type 2
By Ronald Steriti, ND, PhD
This brief review focuses on several studies that show the plant alkaloid berberine can lower
blood glucose as ef ectively as the drug metformin at similar doses (500 mg 3x/day). Berberine
acts on glucose metabolism through several mechanisms, including (AMP-activated protein
kinase) AMPK and incretins.
Berberine is a plant alkaloid found in Hydrastis canadensis
3.3 mmol/L (10.5 mmol/L) (37.8; 135 and 59.4; 189 mg/
enseal), Coptis chinensis
(Coptis or goldenthread), Berberis aqui-
dl) below the baseline, respectively, and remained at this
(Oregon grape), Berberis vulgaris
(barberry), and Berberis
(tree turmeric). It has a long history of medicinal use in
• Hemoglobin A1c decreased from 8.1% to 7.3%.
• Fasting plasma insulin was reduced by 28.1%.
Berberine has a wide range of effects that include antimi-
• The homeostasis model assessment of insulin resistance
crobial (against bacterial diarrhea, intestinal parasites, fungal
infections, Candida albicans
, yeast, and possibly methicillin-
• Total cholesterol and low-density lipoprotein cholesterol
resistant Staphylococcus aureus
); anti-inflammatory; and
During the trial, 20 (34.5%) patients experienced tran-
sient gastrointestinal adverse effects. Functional liver or kidney
Berberine for Diabetes Mellitus Type 2
damages were not observed in any patients.
Berberine has been shown to lower elevated blood glucose as
Another study published in the Journal of Clinical Endo-
effectively as metformin (500 mg 3x/day of each). Two studies
showed that berberine benefits type
on this topic were published in Metabolism
.4 In study A, 36 2 diabetes.5 One hundred sixteen patients with type 2 adults with newly diagnosed type 2 diabetes mellitus were
diabetes and dyslipidemia were randomly allocated to receive
randomly assigned to treatment with berberine or metformin
berberine (1.0 g daily) or placebo for 3 months. In the
(500 mg 3x/day) in a 3-month trial. The hypoglycemic effect of
berberine was similar to that of metformin. Significant changes
• fasting plasma glucose decreased from 7.0 to 5.6 mm/L
• Hemoglobin A1c decreased from 9.5% to 7.5%.
• post-load plasma glucose decreased from 12.0 to 8.9
• Fasting blood glucose (FBG) decreased from 10.6 to 6.9
• Postprandial blood glucose (PBG) decreased from 19.8 to
• triglycerides decreased from 2.51 to 1.61 mm/L (220 to
• Plasma triglycerides from 1.13 to 0.89 mmol/L (100.5 to
• total cholesterol decreased from 5.31 to 4.35 mm/L (205
In study B, 48 adults with poorly controlled type 2 diabetes
• LDL cholesterol decreased from 3.23 to 2.55 mm/L
mellitus were supplemented with berberine in a 3-month trial:
• In the first 7 days of treatment, berberine led to a reduction
The glucose disposal rate was increased after berberine treat-
in FBG from 9.6 to 7.8 mmol/L (172.8 to 140.4 mg/dl) and ment (P
=0.037), although no significant change was found PBG from 14.8 to 11.7 mmol/ L (266.4 to 210.6 mg/dl).
between berberine and placebo groups (P
=0.063). Mild to
• During the second week, FBG and PBG declined further, moderate constipation was observed in 5 participants in the
reached a nadir that was 2.1 mmol/L (7.5 mmol/L) and
2010 Natural Medicine Journal 2(10), October 2010 | Page 5
Mechanism of Action
acts through several mechanisms, including mimicking insulin;
Berberine has been found to act on glucose metabolism through
improving insulin action by activating AMPK; reducing insulin
resistance through protein kinase C-dependent up-regulation of
insulin receptor expression; inducing glycolysis; and on incre-
• Improving insulin action by activating AMPK7,8,9,10
tins by promoting GLP-1 secretion and modulating its release,
• Reducing insulin resistance through protein kinase
C-dependent up-regulation of insulin receptor expression11,12
About the Author
• Promoting GLP-1 secretion and modulating its release14,15
Ronald Steriti, ND, is a researcher for Dr.
Jonathan V. Wright, director of the Tahoma Clinic and Meridian Valley Labs. Steriti is a
AMP-Activated Protein Kinase
graduate of the Southwest College of Naturo-
The enzyme 5' adenosine monophosphate-activated protein
kinase (AMPK) plays a role in cellular energy homeostasis. References
AMPK is expressed in a number of tissues, including the liver, brain, and skeletal muscle.
Berberine. Altern Med Rev.
AMPK acts as a “metabolic master switch” that regulates 2
several intracellular systems, including the cellular uptake of
Yu HH, Kim KJ, Cha JD, et al. Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylo-
glucose, the beta-oxidation of fatty acids, and the biogenesis of
coccus aureus. J Med Food.
Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes
The net effect of AMPK activation is stimulation of hepatic
. May 2008;57(5):712-717.
fatty acid oxidation and ketogenesis; inhibition of cholesterol
Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipid-emia with the natural plant alkaloid berberine. J Clin Endocrinol Metab
synthesis, lipogenesis, and triglyceride synthesis; inhibition
of adipocyte lipolysis and lipogenesis; stimulation of skeletal 6
Chen C, Zhang Y, Huang C. Berberine inhibits PTP1B activity and mimics
muscle fatty acid oxidation and muscle glucose uptake; and
insulin action. Biochem Biophys Res Commun
. Jul 2 2010;397(3):543-547.
modulation of insulin secretion by pancreatic beta-cells.18
Turner N, Li JY, Gosby A, et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a
mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes.
Incretins are a group of gastrointestinal hormones that cause a
Lee YS, Kim WS, Kim KH, et al. Berberine, a natural plant product, activates
short-term increase in the amount of insulin released from the
AMP-activated protein kinase with beneficial metabolic effects in diabetic and
beta cells of the islets of Langerhans after eating, which antici-
insulin-resistant states. Diabetes.
pates the postprandial increase in blood glucose. They also slow
Ma X, Egawa T, Kimura H, et al. Berberine-induced activation of 5’-adenosine monophosphate-activated protein kinase and glucose transport in rat skeletal
the rate of absorption of nutrients into the blood stream by
. Apr 26 2010.
reducing gastric emptying and may directly reduce food intake. 10 Hwang JT, Kwon DY, Yoon SH. AMP-activated protein kinase: a potential target In addition, they inhibit glucagon release from the alpha cells
for the diseases prevention by natural occurring polyphenols. N Biotechnol
of the islets of Langerhans. There are 2 main incretins: GLP-1
(glucagon-like peptide-1) and GIP (gastric inhibitory peptide).
11 Zhang H, Wei J, Xue R, et al. Berberine lowers blood glucose in type 2 diabetes
mellitus patients through increasing insulin receptor expression. Metabolism
Both GLP-1 and GIP are rapidly inactivated by the enzyme
12 Kong WJ, Zhang H, Song DQ, et al. Berberine reduces insulin resistance
Several approved drugs act on incretins. Exenatide (Byetta) is
through protein kinase C-dependent up-regulation of insulin receptor expres-sion. Metabolism.
a synthetic version of exendin-4, a hormone found in the saliva 13 Yin J, Gao Z, Liu D, Liu Z, Ye J. Berberine improves glucose metabo-
of the Gila monster with biological properties similar to GLP-1.
lism through induction of glycolysis. Am J Physiol Endocrinol Metab.
Liraglutide (Victoza) is a long-acting GLP-1 analog. Januvia
(Sitagliptin) and Onglyza (Saxagliptin) are DPP-4 inhibitors.
14 Lu SS, Yu YL, Zhu HJ, et al. Berberine promotes glucagon-like peptide-1
(7-36) amide secretion in streptozotocin-induced diabetic rats. J Endocrinol
Transient gastrointestinal adverse effects with berberine were
15 Yu Y, Liu L, Wang X, Liu X, Xie L, Wang G. Modulation of glucagon-like
peptide-1 release by berberine: in vivo and in vitro studies. Biochem Pharmacol
fairly common and may be related to its antimicrobial action.
Berberine may be particularly useful in cases involving both 16 Al-masri IM, Mohammad MK, Tahaa MO. Inhibition of dipeptidyl peptidase
IV (DPP IV) is one of the mechanisms explaining the hypoglycemic effect of berberine. J Enzyme Inhib Med Chem.
Berberine should be avoided in pregnancy.19
17 Winder WW, Hardie DG. AMP-activated protein kinase, a metabolic master
switch: possible roles in type 2 diabetes. Am J Physiol
. Jul 1999;277(1 Pt 1):E1-10.
18 Viollet B, Mounier R, Leclerc J, Yazigi A, Foretz M, Andreelli F. Targeting AMP-
Berberine (at doses of 500 and 1,000 mg 3x/day) has been shown
activated protein kinase as a novel therapeutic approach for the treatment of
to have a significant beneficial effect on diabetes mellitus type 2,
metabolic disorders. Diabetes Metab
. Dec 2007;33(6):395-402.
and may be as effective as metformin (500 mg 3x/day). Berberine
19 Berberine. Altern Med Rev.
2010 Natural Medicine Journal 2(10), October 2010 | Page 6
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