Abstract
The caveolin family of the membrane anchoring proteins accumulates various growth receptors in caveolae and inhibits their function. Here, we identify caveolin as a potent enhancer of insulin signal when overexpressed in the liver in vivo, where endogenous caveolin is little expressed. Adenovirus-mediated caveolin-3 gene transfer to the liver led to a marked increase in hepatic glycogen synthesis in diabetic mice (p<0.05, n=4), but not in non-diabetic lean mice, and was accompanied by a decrease in mRNA expression of phosphoenlopyruvate carboxykinase (p<0.05, n=5) and an increase in that of glucokinase (p<0.05, n=5). There was a marked increase in insulin sensitivity in diabetic obese mice as exemplified by decreased fasting blood glucose levels (p<0.05, n=8) and improved glucose tolerant test performance. These effects were attributed mostly to increased insulin receptor activity and caveolin-mediated, direct inhibition of PTP1B activity (p<0.05, n=4), of which expression was significantly increased in obese mouse liver (p<0.05, n=4). Overexpression of caveolin-3 in hepatic cells enhanced the insulin signal as well. Our results suggest that caveolin-3 is an important, endogenous regulator of glucose metabolism that can enhance insulin signal, in particular, under pathological conditions where phosphatase activity is upregulated. [J Physiol Sci. 2007;57 Suppl:S119]
