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

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 ß-islets. However, little is known about the regulation of Sirt1 and mir-9 levels in pancreatic ß-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 ß-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 ß-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 ß-cells.