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Sulfatide Controls Insulin Secretion by Modulation of ATP-sensitive K⁺-Channel Activity and Ca²⁺-Dependent Exocytosis in Rat Pancreatic ß-Cells

¹ Bartholin Instituttet, Kommunehospitalet, Copenhagen, Denmark
² Laboratory of Islet Cell Physiology, Novo Nordisk, Bagsværd, Denmark
³ Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
⁴ Department of Clinical Neuroscience, Section of Neurochemistry, University of Göteborg, Mölndals Hospital, Mölndal, Sweden

The glycosphingolipid sulfatide is present in secretory granules and at the surface of pancreatic ß-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 ß-cells. No effect of sulfatide was observed on whole-cell Ca²⁺-channel activity or glucose-induced elevation of cytoplasmic Ca²⁺ concentration. It is interesting that sulfatide stimulated Ca²⁺-dependent exocytosis determined by capacitance measurements and depolarized-induced insulin secretion from islets exposed to diazoxide and high external KCl. The monoclonal sulfatide antibody Sulph I as well as ASA-positive serum reduced glucose-induced insulin secretion by inhibition of Ca²⁺-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 ß-cells.

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