Abstract
Insulin treatment was confirmed to reduce insulin resistance, but the underlying mechanism remains unknown. Caveolin-1 (Cav-1) is a functional protein of the membrane lipid rafts, known as caveolae, and is widely expressed in mammalian adipose tissue. There is increasing evidence that show the involvement of Cav-1 in the AKT activation, which is responsible for insulin sensitivity. Our aim was to investigate the effect of Cav-1 depletion on insulin sensitivity and AKT activation in glargine-treated type 2 diabetic mice. Mice were exposed to a high-fat diet and subject to intraperitoneal injection of streptozotocin to induce diabetes. Next, glargine was administered to treat T2DM mice for 3 weeks (insulin group). The expression of Cav-1 was then silenced by injecting lentiviral-vectored short hairpin RNA (shRNA) through the tail vein of glargine-treated T2DM mice (CAV1-shRNA group), while scramble virus injection was used as a negative control (Ctrl-shRNA group). The results showed that glargine was able to upregulate the expression of PI3K and activate serine phosphorylation of AKT through the upregulation of Cav-1 expression in paraepididymal adipose tissue of the insulin group. However, glargine treatment could not activate AKT pathway in Cav-1 silenced diabetic mice. These results suggest that Cav-1 is essential for the activation of AKT and improving insulin sensitivity in type 2 diabetic mice during glargine treatment.
Highlights
Insulin resistance plays an important role in the occurrence and development of type 2 diabetes mellitus (T2DM) [1]
Impaired insulin sensitivity was verified by intraperitoneal insulin tolerance test (IPITT)
The impaired glucose tolerance of mice was verified by intraperitoneal glucose tolerance test (IPGTT)
Summary
Insulin resistance plays an important role in the occurrence and development of type 2 diabetes mellitus (T2DM) [1]. Intensive insulin therapy has been reported to delay or even partially restore the development of type 2 diabetes mellitus by improving insulin resistance (IR) [2, 3]. Visceral adipose tissue is a vital insulin responsive organ and has been confirmed to be positively correlated with insulin resistance [4]. Improving insulin responsiveness of visceral fat has been regarded as an effective way to alleviate insulin resistance. We found a reduction of caveolin-1 mRNA in the omental adipose tissue of overweight patients [12]. Taken together, these results suggest that Cav-1 is responsile for insulin sensitivity.
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