A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice.

Details

Serval ID
serval:BIB_BDCD70C7E210
Type
Article: article from journal or magazin.
Collection
Publications
Title
A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice.
Journal
Diabetes
Author(s)
Roduit R., Masiello P., Wang S.P., Li H., Mitchell G.A., Prentki M.
ISSN
0012-1797 (Print)
ISSN-L
0012-1797
Publication state
Published
Issued date
09/2001
Peer-reviewed
Oui
Volume
50
Number
9
Pages
1970-1975
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Endogenous lipid stores are thought to be involved in the mechanism whereby the beta-cell adapts its secretory capacity in obesity and diabetes. In addition, hormone-sensitive lipase (HSL) is expressed in beta-cells and may provide fatty acids necessary for the generation of coupling factors linking glucose metabolism to insulin release. We have recently created HSL-deficient mice that were used to directly assess the role of HSL in insulin secretion and action. HSL(-/-) mice were normoglycemic and normoinsulinemic under basal conditions, but showed an approximately 30% reduction of circulating free fatty acids (FFAs) with respect to control and heterozygous animals after an overnight fast. An intraperitoneal glucose tolerance test revealed that HSL-null mice were glucose-intolerant and displayed a lack of a rise in plasma insulin after a glucose challenge. Examination of plasma glucose during an insulin tolerance test suggested that HSL-null mice were insulin-resistant, because plasma glucose was barely lowered after the injection of insulin. Freshly isolated islets from HSL-deficient mice displayed elevated secretion at low (3 mmol/l) glucose, failed to release insulin in response to high (20 mmol/l) glucose, but had a normal secretion when challenged with elevated KCl. The phenotype of heterozygous mice with respect to the measured parameters in vitro was similar to that of wild type. Finally, the islet triglyceride content of HSL(-/-) mice was 2-2.5 fold that in HSL(-/+) and HSL(+/+) animals. The results demonstrate an important role of HSL and endogenous beta-cell lipolysis in the coupling mechanism of glucose-stimulated insulin secretion. The data also provide direct support for the concept that some lipid molecule(s), such as FFAs, fatty acyl-CoA or their derivatives, are implicated in beta-cell glucose signaling.

Keywords
Animals, Blood Glucose/metabolism, Glucose/pharmacology, Glucose/physiology, Glucose Intolerance/etiology, Hypoglycemic Agents/pharmacology, In Vitro Techniques, Insulin/pharmacology, Insulin/secretion, Islets of Langerhans/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout/genetics, Reference Values, Sterol Esterase/deficiency, Sterol Esterase/genetics, Sterol Esterase/physiology, Triglycerides/metabolism
Pubmed
Web of science
Create date
20/09/2017 13:24
Last modification date
20/08/2019 15:32
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