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.
Gao
Hong
H
Shanghai Clinical Center for Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, 197 Rui-Jin 2nd Road, Shanghai, 200025, China.
Wang
Xinjun
X
Zhang
Zhiguo
Z
Yang
Yisheng
Y
Yang
Jun
J
Li
Xiaoying
X
Ning
Guang
G
D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D051379:Mice; D010455:Peptides / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha; D015854:Up-Regulation; D014688:Venoms / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010455:Peptides; C495693:Slc2a4 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D011972:Receptor, Insulin; D005947:Glucose