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Pancreatic β-Cell Lipoprotein Lipase Independently Regulates Islet Glucose Metabolism and Normal Insulin Secretion.
- Source :
-
Journal of Biological Chemistry . 3/11/2005, Vol. 280 Issue 10, p9023-9029. 7p. 3 Diagrams, 1 Chart, 18 Graphs. - Publication Year :
- 2005
-
Abstract
- Lipid and glucose metabolism are adversely affected by diabetes, a disease characterized by pancreatic β-cell dysfunction. To clarify the role of lipids in insulin secretion, we generated mice with β-cell-specific overexpression (βLPL-TG) or inactivation (βLPL-KO) of lipoprotein lipase (LPL), a physiologic provider of fatty acids. LPL enzyme activity and triglyceride content were increased in βLPL-TG islets; decreased LPL enzyme activity in βLPL-KO islets did not affect islet triglyceride content. Surprisingly, both βLPL-TG and βLPL-KO mice were strikingly hyperglycemic during glucose tolerance testing. Impaired glucose tolerance in βLPL-KO mice was present at one month of age, whereas βLPL-TG mice did not develop defective glucose homeostasis until approximately five months of age. Glucose-simulated insulin secretion was impaired in islets isolated from both mouse models. Glucose oxidation, critical for ATP production and triggering of insulin secretion mediated by the ATP-sensitive potassium (KATP) channel, was decreased in βLPL-TG islets but increased in βLPL-KO islets. Islet ATP content was not decreased in either model. Insulin secretion was defective in both βLPL-TG and βLPL-KO islets under conditions causing calcium-dependent insulin secretion independent of the KATP channel. These results show that β-cell-derived LPL has two physiologically relevant effects in islets, the inverse regulation of glucose metabolism and the independent mediation of insulin secretion through effects distal to membrane depolarization. [ABSTRACT FROM AUTHOR]
- Subjects :
- *DIABETES
*PANCREATIC beta cells
*LIPIDS
*GLUCOSE
*METABOLISM
*FATTY acids
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 280
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16583882
- Full Text :
- https://doi.org/10.1074/jbc.M409706200