Antidiabetic activity of resveratrol, a known SIRT1 activator in a genetic model for type-2 diabetes.
In the present study, resveratrol, a polyphenolic SIRT1 activator was evaluated for its SIRT1 activation in an in vitro fluorescent based assay (EC(50) : 7 μM). The efficacy of resveratrol was also evaluated in ob/ob mice for its antidiabetic and associated metabolic effects. Mice aged 5-8 weeks were included in four groups; control and resveratrol at 5, 15, 50 mg/kg, b.i.d. and were dosed orally. After 4 weeks of drug treatment, body weights were noted and random blood glucose and insulin was estimated for the antidiabetic effect. Animals were also subjected to the oral glucose tolerance test to observe any improvement in the glucose excursion. Triglycerides, total cholesterol, adiponectin and free fatty acid levels were also estimated. The results showed that resveratrol exhibited significant antihyperglycemic activity with an improvement in the insulin levels compared with the control mice. There was also a significant improvement observed in the glucose excursion in the oral glucose tolerance test performed for 120 min; although an insignificant improvement in the triglycerides, total cholesterol, adiponectin and free fatty acid levels was observed at different doses of resveratrol tested. The present findings suggest that resveratrol is an antihyperglycemic agent and drugs similar to resveratrol can be considered as an effective therapeutic adjuvant for the current treatment of diabetes mellitus.
Sharma
Sameer
S
Department of Pharmacology, New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana, India. sameer.sharma@ranbaxy.com
Misra
Chandra Sekhar
CS
Arumugam
Surendar
S
Roy
Subhasis
S
Shah
Vanya
V
Davis
Joseph Alex
JA
Shirumalla
Raj Kumar
RK
Ray
Abhijit
A
D052242:Adiponectin / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D051379:Mice; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D013267:Stilbenes; D014280:Triglycerides; D002784:Cholesterol; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005947:Glucose; D000077185:Resveratrol