IGF-I regulates IRS-1 expression in 3T3-L1 adipocytes.
IRS-1 (the insulin receptor substrate-1) is required for signaling by both insulin and IGF-I. Chronic treatment of 3T3-L1 adipocytes with insulin at all concentrations results in increased proteolysis of IRS-1. In contrast, treatment with low concentrations of IGF-I (EC50 = 625 pM) for 4 h caused an increase in IRS-1 to 170% of control. Actinomycin D and cycloheximide blocked the IGF-I effect, but not the insulin effect, suggesting that IGF-I stimulated the synthesis of IRS-1. Concentrations of IGF-I high enough to cause significant binding to the insulin receptor resulted in the down-regulation of IRS-1. Phosphatidylinositol 3'-kinase inhibitors blocked both the insulin and IGF-I effects. Chronic IGF-I treatment caused an increase in both acute insulin-stimulated dGlc uptake and acute IGF-I-stimulated dGlc uptake. Chronic insulin treatment caused a decrease in both acute insulin-stimulated dGlc uptake and acute IGF-I-stimulated dGlc uptake.
Department of Internal Medicine, Texas Tech University Health Sciences Center, 3601 Fourth Street, Lubbock, 79430, USA.
K M
KM
Rice
C W
CW
Garner
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D011972:Receptor, Insulin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D002867:Chromones; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010750:Phosphoproteins; D003609:Dactinomycin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007334:Insulin-Like Growth Factor I; D003513:Cycloheximide; D011972:Receptor, Insulin; D005947:Glucose