Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone.

Abstract

AIM:

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: K J Nadeau, L B Ehlers, L E Aguirre, J E B Reusch, B Draznin
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 9 Issue 5 Pg. 714-23 (Sep 2007) ISSN: 1462-8902 [Print] England
• PMID: 17697064 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Blood Glucose
• Fatty Acids
• Hypoglycemic Agents
• Hypolipidemic Agents
• Insulin
• PPAR alpha
• SREBF1 protein, human
• Sterol Regulatory Element Binding Protein 1
• Thiazolidinediones
• Triglycerides
• Rosiglitazone
• Fenofibrate

Topics

• Animals
• Blood Glucose (drug effects, metabolism)
• Fatty Acids (metabolism)
• Fenofibrate (pharmacology, therapeutic use)
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Hypolipidemic Agents (pharmacology, therapeutic use)
• Insulin (blood)
• PPAR alpha
• Rats
• Rats, Zucker (anatomy & histology, metabolism)
• Rosiglitazone
• Sterol Regulatory Element Binding Protein 1
• Thiazolidinediones (pharmacology, therapeutic use)
• Triglycerides (metabolism)