The Metabolisable Hexoses D-Glucose and D-Mannose Enhance the Expression of IRS-2 but not of IRS-1 in Pancreatic β-Cells

Abstract

D-glucose regulates maintenance and function of pancreatic β-cells. Several studies have shown that IRS-2, but not IRS-1, is necessary to maintain and sufficient to expand functional β-cell mass. We therefore analyzed the expression of IRS-2 and IRS-1 in β-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.

Key words

IRS-2 - diabetes - β-cells - pancreatic islets

References

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1 Authors contributed equally to this work.