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Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone.
Diabetes Obes Metab. 2007 Sep; 9(5):714-23.DO

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+Show Affiliations

Division of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, CO, USA. nadeaukj@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17697064

Citation

Nadeau, K J., et al. "Discordance Between Intramuscular Triglyceride and Insulin Sensitivity in Skeletal Muscle of Zucker Diabetic Rats After Treatment With Fenofibrate and Rosiglitazone." Diabetes, Obesity & Metabolism, vol. 9, no. 5, 2007, pp. 714-23.
Nadeau KJ, Ehlers LB, Aguirre LE, et al. Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone. Diabetes Obes Metab. 2007;9(5):714-23.
Nadeau, K. J., Ehlers, L. B., Aguirre, L. E., Reusch, J. E., & Draznin, B. (2007). Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone. Diabetes, Obesity & Metabolism, 9(5), 714-23.
Nadeau KJ, et al. Discordance Between Intramuscular Triglyceride and Insulin Sensitivity in Skeletal Muscle of Zucker Diabetic Rats After Treatment With Fenofibrate and Rosiglitazone. Diabetes Obes Metab. 2007;9(5):714-23. PubMed PMID: 17697064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discordance between intramuscular triglyceride and insulin sensitivity in skeletal muscle of Zucker diabetic rats after treatment with fenofibrate and rosiglitazone. AU - Nadeau,K J, AU - Ehlers,L B, AU - Aguirre,L E, AU - Reusch,J E B, AU - Draznin,B, PY - 2007/8/19/pubmed PY - 2007/12/15/medline PY - 2007/8/19/entrez SP - 714 EP - 23 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 9 IS - 5 N2 - 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. SN - 1462-8902 UR - https://www.unboundmedicine.com/medline/citation/17697064/Discordance_between_intramuscular_triglyceride_and_insulin_sensitivity_in_skeletal_muscle_of_Zucker_diabetic_rats_after_treatment_with_fenofibrate_and_rosiglitazone_ L2 - https://doi.org/10.1111/j.1463-1326.2006.00696.x DB - PRIME DP - Unbound Medicine ER -