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- Title
C16:0 Sulfatide Inhibits Insulin Secretion in Rat β-Cells by Reducing the Sensitivity of K<sub>ATP</sub> Channels to ATP Inhibition.
- Authors
Buschard, Karsten; Blomqvist, Maria; Månsson, Jan-Eric; Fredman, Pam; Juhl, Kirstine; Gromada, Jesper
- Abstract
Sulfatide (3'-sulfo-beta;-galactosyl ceramide) is a glycosphingolipid present in mammalians in various fatty acid isoforms of which the saturated 16 carbon-atom length (C16:0) is more abundant in pancreatic islets than in neural tissue, where long-chain sulfatide isoforms dominate. We previously reported that sulfatide isolated from pig brain inhibits glucose-induced insulin secretion by activation of ATP-sensitive K+ channels (KATP channels). Here, we show that C16:0 sulfatide is the active isoform. It inhibits glucose-stimulated insulin secretion by reducing the sensitivity of the KATP channels to ATP. (The half-maximal inhibitory concentration is 10.3 and 36.7 µmol/l in the absence and presence of C16:0 sulfatide, respectively.) C16:0 sulfatide increased whole-cell KATP currents at intermediate glucose levels and reduced the ability of glucose to induce membrane depolarization, reduced electrical activity, and increased the cytoplasmic free Ca2+ concentration. Recordings of cell capacitance revealed that C16:0 sulfatide increased Ca2+-induced exocytosis by 215%. This correlated with a stimulation of insulin secretion by C16:0 sulfatide in intact rat islets exposed to diazoxide and high K+. C24:0 sulfatide or the sulfatide precursor, β-galactosyl ceramide, did not affect any of the measured parameters. C16:0 sulfatide did not modulate glucagon secretion from intact rat islets. In βTC3 cells, sulfatide was expressed (mean [±SD] 0.30 ± 0.04 pmol/µg protein), and C16:0 sulfatide was found to be the dominant isoform. No expression of sulfatide was detected in αTC1-9 cells. We conclude that a major mechanism by which the predominant sulfatide isoform in β-cells, C16:0 sulfatide, inhibits glucose-induced insulin secretion is by reducing the KATP channel sensitivity to the ATP block. Diabetes 55:2826-2834, 2006
- Subjects
GLYCOSPHINGOLIPIDS; FATTY acids; ISLANDS of Langerhans; ADENOSINE triphosphate; ADENINE nucleotides
- Publication
Diabetes, 2006, Vol 55, Issue 10, p2826
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db05-1355