Abstract
Resistin is an adipocyte hormone that modulates glucose homeostasis. Here we show that in 3T3-L1 adipocytes, resistin attenuates multiple effects of insulin, including insulin receptor (IR) phosphorylation, IR substrate 1 (IRS-1) phosphorylation, phosphatidylinositol-3-kinase (PI3K) activation, phosphatidylinositol triphosphate production, and activation of protein kinase B/Akt. Remarkably, resistin treatment markedly induces the gene expression of suppressor of cytokine signaling 3 (SOCS-3), a known inhibitor of insulin signaling. The 50% effective dose for resistin induction of SOCS-3 is approximately 20 ng/ml, close to levels of resistin in serum. Association of SOCS-3 protein with the IR is also increased by resistin. Inhibition of SOCS function prevented resistin from antagonizing insulin action in adipocytes. SOCS-3 induction is the first cellular effect of resistin that is independent of insulin and is a likely mediator of resistin's inhibitory effect on insulin signaling in adipocytes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3-L1 Cells
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Adipocytes / cytology
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Adipocytes / drug effects
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Adipocytes / metabolism*
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Animals
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Cell Differentiation / physiology
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Cells, Cultured
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Enzyme Activation / drug effects
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Enzyme Activation / physiology*
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Hormones, Ectopic / administration & dosage
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Hormones, Ectopic / pharmacology*
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Insulin / metabolism
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Insulin Receptor Substrate Proteins
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Insulin Resistance / physiology*
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Mice
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoproteins / metabolism
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Phosphorylation / drug effects
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Receptor, Insulin / metabolism
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Repressor Proteins / metabolism*
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Resistin
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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Transcription Factors / metabolism*
Substances
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Hormones, Ectopic
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Insulin
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Insulin Receptor Substrate Proteins
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Irs1 protein, mouse
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Phosphoproteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Resistin
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Retn protein, mouse
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SOCS3 protein, human
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Suppressor of Cytokine Signaling 3 Protein
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Suppressor of Cytokine Signaling Proteins
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Transcription Factors
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Receptor, Insulin
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt