Caveolin-1 Was Required for Glargine to Improve Insulin Sensitivity and Activate PI3K/AKT Pathway in Visceral Adipose Tissue of Type 2 Diabetic Mice

Abstract

Insulin treatment improves insulin sensitivity, but the underlying mechanism remains unknown. Caveolin-1(Cav-1) konckout mice present insulin resistance.Our aim is to investigate the effect of Cav-1 depletion on insulin sensitivity and PI3K/AKT activation in glargine treatment of type 2 diabetic mice. C57BL/6J mice were divided into five groups(n=5 for each group).We firstly used high-fat high-carbonhydrate diet with intraperitoneal injection of streptozotocin(40mg/kg for 3 days) to induce type 2 diabetic(T2DM group) mice. Next, glargine was started at a dose of 0.4u/day to T2DM mice for 3 weeks(Insulin group).Lastly, Cav-1 expression was silenced by lentiviral-vectored short hairpin RNA (shRNA) through tail vein injection in glargine treated T2DM mice(CAV1-shRNA group) with scramble virus injection as a negative control(Ctrl-shRNA group). As a result, improvement of insulin sensitivity and PI3K/AKT activation with upregulation of Cav-1 were observed in visceral adipose tissue of Insulin group compared with T2DM group (P<0.05). In CAV1-shRNA group,impairment of insulin tolerance and PI3K/AKT activation couldn’t be improved by glargine compared with Ctrl-shRNA group (P<0.05). Our findings suggest that Cav-1 is required for insulin to improve insulin sensitivity and PI3K/AKT activation. More studies are needed to elucidate the mechanism. Disclosure H. Peng: None. H. Li: None. S. Lin: None. W. Zeng: None. C. Lin: None. K. Lin: None. L. Zeng: None.