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- Title
Sulfatide controls insulin secretion by modulation of ATP-sensitive K(+)-channel activity and Ca(2+)-dependent exocytosis in rat pancreatic beta-cells.
- Authors
Buschard, Karsten; Høy, Marianne; Bokvist, Krister; Olsen, Hervør L.; Madsbad, Sten; Fredman, Pam; Gromada, Jesper; Høy, Marianne; Olsen, Hervør L
- Abstract
The glycosphingolipid sulfatide is present in secretory granules and at the surface of pancreatic beta-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 beta-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 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 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 beta-cells.
- Subjects
METACHROMATIC leukodystrophy; GLYCOSPHINGOLIPIDS; ADENOSINE triphosphate
- Publication
Diabetes, 2002, Vol 51, Issue 8, p2514
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.51.8.2514