GLP-1 amplifies insulin signaling by up-regulation of IRbeta, IRS-1 and Glut4 in 3T3-L1 adipocytes.

Glucagon-like peptide-1 (7-36) amide (GLP-1) is an insulin secretagogue. Recently, many studies have shown GLP-1 can improve insulin resistance in peripheral tissues. In the present study, we investigated glucose uptake in 3T3-L1 adipocytes in either basal or insulin resistant state and dissected insulin signaling pathway in order to elucidate the molecular mechanisms of GLP-1 mediated improvement of insulin resistance. We found GLP-1 and its long lasting analogue, exendin 4 up-regulated basal IR, IRS-1 and Glut 4 expressions although they did not increase basal glucose uptake alone. However, GLP-1 and exendin-4 increased insulin mediated glucose uptake in intact and TNF-alpha treated 3T3-L1 adipocytes by up-regulation of phophorylated IRbeta, IRS-1, Akt and GSK-3beta. These results indicate that GLP-1 and its analogue exendin-4 can amplify insulin signaling in 3T3-L1 adipocytes by up-regulation of some crucial insulin signaling molecules.