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C16:0 sulfatide inh...
C16:0 sulfatide inhibits insulin secretion in rat beta-cells by reducing the sensitivity of KATP channels to ATP inhibition
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Buschard, Karsten (author)
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- Blomqvist, Maria K., 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Månsson, Jan-Eric, 1946 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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- Fredman, Pam, 1950 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Juhl, Kirstine (author)
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Gromada, Jesper (author)
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(creator_code:org_t)
- American Diabetes Association, 2006
- 2006
- English.
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:10, s. 2826-34
- Related links:
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http://diabetes.diab...
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https://gup.ub.gu.se...
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https://doi.org/10.2...
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Abstract
Subject headings
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- 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 (K(ATP) channels). Here, we show that C16:0 sulfatide is the active isoform. It inhibits glucose-stimulated insulin secretion by reducing the sensitivity of the K(ATP) channels to ATP. (The half-maximal inhibitory concentration is 10.3 and 36.7 micromol/l in the absence and presence of C16:0 sulfatide, respectively.) C16:0 sulfatide increased whole-cell K(ATP) 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, beta-galactosyl ceramide, did not affect any of the measured parameters. C16:0 sulfatide did not modulate glucagon secretion from intact rat islets. In betaTC3 cells, sulfatide was expressed (mean [+/-SD] 0.30 +/- 0.04 pmol/microg protein), and C16:0 sulfatide was found to be the dominant isoform. No expression of sulfatide was detected in alphaTC1-9 cells. We conclude that a major mechanism by which the predominant sulfatide isoform in beta-cells, C16:0 sulfatide, inhibits glucose-induced insulin secretion is by reducing the K(ATP) channel sensitivity to the ATP block.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Adenosine Triphosphate/*pharmacology
- Animals
- Calcium/metabolism
- Cells
- Cultured
- Exocytosis/drug effects
- Glucose/antagonists & inhibitors
- Insulin/*secretion
- Insulin-Secreting Cells/drug effects/*secretion
- Insulinoma/metabolism
- Membrane Potentials/drug effects
- Oligosaccharides/secretion
- Potassium Channels/*drug effects
- Rats
- Rats
- Inbred Lew
- Sulfoglycosphingolipids/*pharmacology
Publication and Content Type
- ref (subject category)
- art (subject category)
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