抄録
Caveolin, a major structural component of caveolae, is well known to inhibit the function of molecules involved growth factor signal. However, caveolin may exceptionally stimulate insulin signal as implicated in an in vitro experiment using purified recombinant insulin receptor kinase and short caveolin-1 peptides. We have examined the effect of overexpressing caveolin-3, the muscle specific subtype that is not endogenously expressed in the liver, by the use of HepG2 cells, human hepatoma cells, because the liver plays a major role in insulin signal. We used adenovirus harboring caveolin-3 (Ad.cav3) or green fluorescent protein (control, GFP). Caveolin-3 overexpression did not alter the expression of endogenous insulin receptor in HepG2 cells, but significantly increased the phosphorylation of insulin receptor induced by insulin (Ad.cav3 132+18%, control, 100+16%, p<0.05, n=4). Serine phosphorylation of Akt1, a downstream molecule of insulin signal, was also enhanced upon insulin stimulation (Ad.cav3 167+42%, control, 100+10%, p<0.05, n=4). When adenovirus was injected intravenously in mice, GFP was accumulated abundantly in the liver. Putting together, our data suggest that adenovirus-mediated caveolin-3 overexpression augments insulin signal in hepatocytes; this strategy may be utilized in future gene therapy for improving hepatic glucose metabolism in diabetes. [Jpn J Physiol 54 Suppl:S66 (2004)]
