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

Zhou, Y T; Shimabukuro, M; Wang, M Y; Lee, Y; Higa, M; Milburn, J L; Newgard, C B; Unger, R H · Proc Natl Acad Sci U S A · 1998

basic_science · Level V

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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.

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