Involvement of heparan sulfate 3-O-sulfotransferase isoform-1 in the insulin secretion pathway.

Abstract

Aims/Introduction: Heparan sulfate (HS) mediates a variety of molecular recognition events that are essential for differentiation, morphogenesis and homeostasis through various HS forms that result from differential sulfate modification. Recently, we found that HS is localized exclusively around βß-cells in islets of adult mice and is required for insulin secretion. The aim of this study was to examine the contribution of HS sulfate groups to insulin secretion. Glucose-induced insulin secretion (GIIS) was examined in mouse pancreatic islets, the mouse pancreatic β-cell line MIN6 cells and its derivative MIN6T3 cells after removal of sulfate groups by sodium chlorate, a competitive inhibitor of glycosaminoglycan sulfation. Quantitative reverse transcription polymerase chain reaction was used for analyzing messenger ribonucleic acid (mRNA) expression of HS modification enzymes. Expression of HS 3-O-sulfotransferase isoform-1 (Hs3st1) was silenced and GIIS was examined. Impaired insulin secretion by islets, MIN6 cells and MIN6T3 cells was observed after treatment with sodium chlorate. Sodium chlorate-treatment upregulated the mRNA expression of sulfotransferases expressed in MIN6T3 cells. Expression of the Hs3st1 was strongly upregulated by sodium chlorate-treatment, and its silencing by RNA interference reduced GIIS in MIN6T3 cells. Our data suggest that the 3-O-sulfate group of HS that is modified by Hs3st1 plays a significant role(s) in the insulin secretory pathway, selectively through an interaction with factor(s) upstream of membrane depolarization in β-cells. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00205.x, 2012).