Sulfatide Controls Insulin Secretion by Modulation of ATP-sensitive K~+-Channel Activity and Ca~(2+)-Dependent Exocytosis in Rat Pancreatic β-Cells

摘要

The glycosphingolipid sulfatide is present in secretory granules and at the surface of pancreatic β-cells, and antisulfatide antibodies (ASA; IgG1) are found in serum from the majority of patients with newly diagnosed type 1 diabetes. Here we demonstrate that sulfatide produced a glucose- and concentration-dependent inhibition of insulin release from isolated rat pancreatic islets. This inhibition of insulin secretion was due to activation of ATP-sensitive K~+-(K_(ATP)) channels in single rat ?-cells. No effect of sulfatide was observed on whole-cell Ca~(2+)-channel activity or glucose-induced elevation of cytoplasmic Ca~(2+) concentration. It is interesting that sulfatide stimulated Ca~(2+)-dependent exocy-tosis determined by capacitance measurements and depolarized-induced insulin secretion from islets exposed to diazoxide and high external KC1. The monoclonal sulfatide antibody Sulph I as well as ASA-positive serum reduced glucose-induced insulin secretion by inhibition of Ca~(2+)-dependent exocytosis. Our data suggest that sulfatide is important for the control of glucose-induced insulin secretion and that both an increase and a decrease in the sulfatide content have an impact on the secretory capacity of the individual β-cells.