Role of peroxisome proliferator-activated receptor alpha in disease of pancreatic beta cells.
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.
Zhou
Y T
YT
Gifford Laboratories for Diabetes Research, Center for Diabetes Research, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA.
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
D000818:Animals; D001483:Base Sequence; D002994:Clofibrate / Q000378:metabolism / Q000494:pharmacology; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects; D007515:Islets of Langerhans / Q000503:physiopathology*; D020738:Leptin; D008297:Male; D010182:Pancreatic Diseases / Q000503:physiopathology*; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology
D017931:DNA Primers; D020738:Leptin; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014212:Tretinoin; D002994:Clofibrate