Sulfatide controls insulin secretion by modulation of ATP-sensitive K(+)-channel activity and Ca(2+)-dependent exocytosis in rat pancreatic beta-cells.
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.
Buschard
Karsten
K
Bartholin Instituttet, Kommunehospitalet, Copenhagen, Denmark. buschard@dadlnet.dk
Høy
Marianne
M
Bokvist
Krister
K
Olsen
Hervør L
HL
Madsbad
Sten
S
Fredman
Pam
P
Gromada
Jesper
J
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D006017:Glycolipids / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D054086:KATP Channels; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011917:Rats, Inbred Lew; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*
D018528:ATP-Binding Cassette Transporters; D015220:Calcium Channels; D006017:Glycolipids; D007328:Insulin; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D013433:Sulfoglycosphingolipids; C092520:uK-ATP-1 potassium channel; D002118:Calcium