title: Gemfibrozil not fenofibrate decreases systemic glucose level via PPARα.
abstract: BACKGROUND
  Concurrence of high glucose or diabetes in patients with dyslipidemia is presenting major challenges for clinicians. Although sporadically reported, a rational basis for the use of fibrates for the treatment of dyslipidemia with concurrent metabolic syndrome has not been established.
  
  
  METHODS
  In this study, wild-type (WT) and Ppara-null (KO) mice were fed a serial gemfibrozil- and fenofibrate-containing diet under the same experimental conditions for 14 days. Glucose level in the blood, glycogen storage in the liver tissues, and the potential toxic responses were assayed. Genes involved in glucose metabolism were determined by quantitative polymerase chain reaction analysis.
  
  
  RESULTS
  Both the blood glucose level and the glycogen content in the liver were down-regulated by gemfibrozil but not by fenofibrate in WT mice, in a dose-dependent manner. This decrement did not occur in KO mice for either fibrate agent. Secondary regulation on the transcription of pyruvate kinase, and gluconolactonase were observed following gemfibrozil treatment, which was differential between WT mice and KO mice.
  
  
  CONCLUSIONS
  Gemfibrozil, not fenofibrate, down-regulates systemic glucose level and glycogen storage in the liver dependent on PPARα, suggesting its potential value for treatment of dyslipidemia with concurrent diabetes or high glucose levels.
authors.forename: Danjun
authors.initials: D
authors.lastname: Song
authors.forename: Zanbo
authors.initials: Z
authors.lastname: Chu
authors.forename: Luo
authors.initials: L
authors.lastname: Min
authors.forename: Tan
authors.initials: T
authors.lastname: Zhen
authors.forename: Pengxu
authors.initials: P
authors.lastname: Li
authors.forename: Liyuan
authors.initials: L
authors.lastname: Han
authors.forename: Shizhong
authors.initials: S
authors.lastname: Bu
authors.forename: Julin
authors.initials: J
authors.lastname: yang
authors.forename: F J
authors.initials: FJ
authors.lastname: Gonzale
authors.forename: Aiming
authors.initials: A
authors.lastname: Liu
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology*; D015248:Gemfibrozil / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006529:Hepatomegaly / Q000235:genetics / Q000473:pathology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D047493:PPAR alpha / Q000187:drug effects* / Q000235:genetics; D011770:Pyruvate Kinase / Q000096:biosynthesis
chemical_list: D000960:Hypolipidemic Agents; D047493:PPAR alpha; D006003:Glycogen; D011770:Pyruvate Kinase; D005947:Glucose; D015248:Gemfibrozil; D011345:Fenofibrate