The metabolisable hexoses D-glucose and D-mannose enhance the expression of IRS-2 but not of IRS-1 in pancreatic beta-cells.
D-glucose regulates maintenance and function of pancreatic beta-cells. Several studies have shown that IRS-2, but not IRS-1, is necessary to maintain and sufficient to expand functional beta-cell mass. We therefore analyzed the expression of IRS-2 and IRS-1 in beta-cells after culture in the presence of various concentrations of D-glucose and other metabolisable or non-metabolisable hexoses. D-glucose increased Irs-2 transcription and IRS-2 accumulation in a dose-dependent manner (1.6 to 25 mmol/l), with a 3-fold increased plateau after 10 h. In contrast, the expression of IRS-1 remained unaffected. D-glucose also induced phosphorylation of IRS-2 while non-metabolisable hexoses did neither affect expression nor phosphorylation. D-glucose-mediated elevation and phosphorylation of IRS-2 were independent of autocrine insulin action although insulin itself could transiently and slightly enhance IRS-2 expression.
Amacker-Françoys
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Division of Endocrinology and Diabetes, University Hospital, Zurich, Switzerland.
Mohanty
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S
Niessen
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Spinas
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GA
Trüb
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T
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D050417:Insulin-Secreting Cells / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008358:Mannose / Q000378:metabolism / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D005947:Glucose; D008358:Mannose