Caveolin-1 Is Essential for the Improvement of Insulin Sensitivity through AKT Activation during Glargine Treatment on Diabetic Mice

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.

Leptin‐dependent differential remodeling of visceral and pericardial adipose tissue following chronic exercise and psychosocial stress

“…Mechanistically, caveolin has been shown to regulate insulin sensitivity through the PI3K/Akt pathway in VAT and caveolin-1 knockout mice develop significant insulin resistance. 65 Although we did not see any major effects of stress on insulin signaling in VAT, previous work has shown that chronic stress impairs insulin signaling and glucose uptake in VAT in response to insulin stimulation in Fisher rats; but upregulates the intracellular signaling molecules that respond to inflammatory signals through p65 and p38 and subsequently inhibit the phosphorylation of IRS-1. 66 Our data suggest that psychosocial stress was also associated with increased adipogenesis in the absence of leptin signaling suggesting a role in pre-adipocyte expansion.…”

“…Interestingly, the increase in insulin sensitivity following exercise was associated with an increase in caveolin‐1 expression. Mechanistically, caveolin has been shown to regulate insulin sensitivity through the PI3K/Akt pathway in VAT and caveolin‐1 knockout mice develop significant insulin resistance 65 . Although we did not see any major effects of stress on insulin signaling in VAT, previous work has shown that chronic stress impairs insulin signaling and glucose uptake in VAT in response to insulin stimulation in Fisher rats; but upregulates the intracellular signaling molecules that respond to inflammatory signals through p65 and p38 and subsequently inhibit the phosphorylation of IRS‐1 66 .…”

The importance of caveolin as a target in the prevention and treatment of diabetic cardiomyopathy

“…However, under the influence of obesity-related risk factors, insulin sensitivity still decreases and eventually insulin resistance develops ( 139 ). The latest study results suggested that insulin treatment significantly upregulated the PI3K/Akt signaling pathway and insulin sensitivity in diabetic mice, while Cav-1 gene silencing eliminated this effect ( 140 ). Consistently, increased expression of Cav-1 in skeletal muscle can also improve insulin sensitivity ( 141 ), which may be related to the positive regulation of IRα and IRS-1 levels by Cav-1 ( 142 ).…”

Fagopyrum tataricum ethanol extract ameliorates symptoms of hyperglycemia by regulating gut microbiota in type 2 diabetes mellitus mice

“…AKT-1 is a serine/threonine protein kinase, it is a key signaling molecule in the process of hypoglycemic activity of insulin and highly expressed in target tissues containing insulin receptors. 15 GLUT-2 is a key regulatory factor of glucose uptake in cells. It affects systemic glucose homeostasis and mediates insulin receptor signal transduction.…”