Abstract
We have devised procedures for decreasing the amount of IRS-1 in 3T3-L1 adipocytes (viz., chronic treatments with insulin, dexamethasone, 1-methyl-3-isobutylxanthine, cycloheximide or actinomycin D) and have determined the correlation between the amounts of IRS-1, insulin receptor, GluT4 and phosphatidylinositol 3'-kinase regulatory subunit with insulin-responsive dGlc transport. Each of these treatments decreased insulin responsiveness that correlated with the amount of IRS-1, but not with the amount of the other signaling proteins or tyrosine-phosphorylated IRS-1. Removal of insulin after chronic treatment resulted in a return of both insulin responsiveness and IRS-1. Increased expression of IRS-1 occurred during differentiation simultaneously with increased insulin-responsive dGlc transport. These data are consistent with a role of IRS-1 in insulin signaling to the glucose transport system.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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3T3 Cells
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Adipocytes / drug effects
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Adipocytes / metabolism*
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Animals
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Biological Transport
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Cell Differentiation
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Cycloheximide / pharmacology
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Dactinomycin / pharmacology
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Deoxyglucose / pharmacokinetics*
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Dexamethasone / pharmacology
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Fibroblasts / physiology
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Glucose Transporter Type 4
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Insulin / metabolism
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Insulin / pharmacology*
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Insulin Receptor Substrate Proteins
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Mice
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Monosaccharide Transport Proteins / metabolism
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Muscle Proteins*
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Phosphatidylinositol 3-Kinases
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Phosphoproteins / deficiency*
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Receptor, Insulin / metabolism
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Signal Transduction*
Substances
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Glucose Transporter Type 4
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Insulin
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Insulin Receptor Substrate Proteins
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Irs1 protein, mouse
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Monosaccharide Transport Proteins
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Muscle Proteins
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Phosphoproteins
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Slc2a4 protein, mouse
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Dactinomycin
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Dexamethasone
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Cycloheximide
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Deoxyglucose
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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Receptor, Insulin
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1-Methyl-3-isobutylxanthine