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Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells.

ABSTRACT: Expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and enzymes of fatty acid (FA) oxidation is markedly reduced in the fat-laden, dysfunctional islets of obese, prediabetic Zucker diabetic fatty (fa/fa) rats with mutated leptin receptors (OB-R). Leptin, PPARalpha/retinoid x receptor ligands, and FA all up-regulate PPARalpha and enzymes of FA oxidation and stimulate [3H]-palmitate oxidation in normal islets but not in islets from fa/fa rats. Overexpression of normal OB-R in islets of fa/fa rats corrects all of the foregoing abnormalities and reverses the diabetic phenotype. PPARalpha is a OB-R-dependent factor required for normal fat homeostasis in islet cells.

SUBMITTER: Zhou YT

PROVIDER: S-EPMC21174 | biostudies-literature | 1998 Jul

REPOSITORIES: biostudies-literature

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Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells.

Zhou Y T YT Shimabukuro M M Wang M Y MY Lee Y Y Higa M M Milburn J L JL Newgard C B CB Unger R H RH

Proceedings of the National Academy of Sciences of the United States of America 19980701 15

Expression of peroxisome proliferator-activated receptor alpha (PPARalpha) and enzymes of fatty acid (FA) oxidation is markedly reduced in the fat-laden, dysfunctional islets of obese, prediabetic Zucker diabetic fatty (fa/fa) rats with mutated leptin receptors (OB-R). Leptin, PPARalpha/retinoid x receptor ligands, and FA all up-regulate PPARalpha and enzymes of FA oxidation and stimulate [3H]-palmitate oxidation in normal islets but not in islets from fa/fa rats. Overexpression of normal OB-R i ...[more]

PMID: 9671776

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