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.
Gifford Laboratories for Diabetes Research, Center for Diabetes Research, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA.
Y T
YT
Zhou
M
M
Shimabukuro
M Y
MY
Wang
Y
Y
Lee
M
M
Higa
J L
JL
Milburn
C B
CB
Newgard
R H
RH
Unger
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