title: Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone.
abstract: OBJECTIVE
  Intramyocellular triglyceride (IMTG) correlates with insulin resistance, but there is no clear causal relationship. Insulin resistance and associated hyperinsulinaemia may increase IMTG, via the insulin-regulated transcription factor, sterol regulatory element-binding protein 1 (SREBP-1). PPAR agonists may also affect IMTG via changes in insulin sensitivity, SREBP-1 or other factors.
  
  
  METHODS
  We examined skeletal muscle IMTG and SREBP-1 expression, and metabolic parameters in Zucker diabetic fatty rats (ZDF) after 25 weeks of PPAR-gamma or PPAR-alpha administration.
  
  
  RESULTS
  Compared with Zucker lean rats (ZL), untreated ZDF had significantly higher weights, serum glucose, insulin, free fatty acids, total cholesterol and triglycerides. IMTG and SREBP-1c messenger RNA (mRNA) were also higher in untreated ZDF; both were decreased by fenofibrate (FF). Rosiglitazone (Rosi), despite marked improvement in glycaemia, hyperinsulinaemia and hyperlipidaemia, failed to affect SREBP-1 expression, and increased body weight and IMTG. Rosi/FF combination caused less weight gain and no IMTG increase, despite metabolic effects similar to Rosi alone.
  
  
  CONCLUSIONS
  IMTG and SREBP-1c mRNA are high in the ZDF. FF and Rosi both improved insulin sensitivity but had opposite effects on IMTG. Thus, there was a clear discordance between insulin sensitivity and IMTG with PPAR agonists, indicating that IMTG and insulin sensitivity do not share a simple relationship.
authors: Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO, USA. nadeaukj@hotmail.com
authors: K J
authors: KJ
authors: Nadeau
authors: L B
authors: LB
authors: Ehlers
authors: L E
authors: LE
authors: Aguirre
authors: J E B
authors: JE
authors: Reusch
authors: B
authors: B
authors: Draznin
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D047493:PPAR alpha; D051381:Rats; D011924:Rats, Zucker / Q000033:anatomy & histology / Q000378:metabolism; D000077154:Rosiglitazone; D051780:Sterol Regulatory Element Binding Protein 1; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D007328:Insulin; D047493:PPAR alpha; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D011345:Fenofibrate