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Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone
Author(s) -
Nadeau K. J.,
Ehlers L. B.,
Aguirre L. E.,
Reusch J. E. B.,
Draznin B.
Publication year - 2007
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2006.00696.x
Subject(s) - medicine , endocrinology , fenofibrate , insulin resistance , rosiglitazone , triglyceride , insulin , metabolic syndrome , type 2 diabetes , biology , diabetes mellitus , cholesterol
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‐γ or PPAR‐α 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.