Sirt1 and mir-9 expression is regulated during glucose-stimulated insulin secretion in pancreatic β-islets

FEBS J. 2011 Apr;278(7):1167-74. doi: 10.1111/j.1742-4658.2011.08042.x. Epub 2011 Mar 4.

Abstract

MicroRNA mir-9 is speculated to be involved in insulin secretion because of its ability to regulate exocytosis. Sirt1 is an NAD-dependent protein deacetylase and a critical factor in the modulation of cellular responses to altered metabolic flux. It has also been shown recently to control insulin secretion from pancreatic β-islets. However, little is known about the regulation of Sirt1 and mir-9 levels in pancreatic β-cells, particularly during glucose-dependent insulin secretion. In this article, we report that mir-9 and Sirt1 protein levels are actively regulated in vivo in β-islets during glucose-dependent insulin secretion. Our data also demonstrates that mir-9 targets and regulates Sirt1 expression in insulin-secreting cells. This targeting is relevant in pancreatic β-islets, where we show a reduction in Sirt1 protein levels when mir-9 expression is high during glucose-dependent insulin secretion. This functional interplay between insulin secretion, mir-9 and Sirt1 expression could be relevant in diabetes. It also highlights the crosstalk between an NAD-dependent protein deacetylase and microRNA in pancreatic β-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Gene Expression Regulation
  • Glucose / pharmacology*
  • HEK293 Cells
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / physiology
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • NIH 3T3 Cells
  • Sequence Alignment
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*

Substances

  • Insulin
  • MIRN9 microRNA, mouse
  • MicroRNAs
  • Sirtuin 1
  • Glucose