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• W2140799114 endingPage "2524" @default.
• W2140799114 startingPage "2514" @default.
• W2140799114 abstract "Diabetic heart failure may be causally associated with alterations in cardiac energy metabolism and insulin resistance. Mice with heart-specific overexpression of peroxisome proliferator–activated receptor (PPAR)α showed a metabolic and cardiomyopathic phenotype similar to the diabetic heart, and we determined tissue-specific glucose metabolism and insulin action in vivo during hyperinsulinemic-euglycemic clamps in awake myosin heavy chain (MHC)-PPARα mice (12–14 weeks of age). Basal and insulin-stimulated glucose uptake in heart was significantly reduced in the MHC-PPARα mice, and cardiac insulin resistance was mostly attributed to defects in insulin-stimulated activities of insulin receptor substrate (IRS)-1–associated phosphatidylinositol (PI) 3-kinase, Akt, and tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). Interestingly, MHC-PPARα mice developed hepatic insulin resistance associated with defects in insulin-mediated IRS-2–associated PI 3-kinase activity, increased hepatic triglyceride, and circulating interleukin-6 levels. To determine the underlying mechanism, insulin clamps were conducted in 8-week-old MHC-PPARα mice. Insulin-stimulated cardiac glucose uptake was similarly reduced in 8-week-old MHC-PPARα mice without changes in cardiac function and hepatic insulin action compared with the age-matched wild-type littermates. Overall, these findings indicate that increased activity of PPARα, as occurs in the diabetic heart, leads to cardiac insulin resistance associated with defects in insulin signaling and STAT3 activity, subsequently leading to reduced cardiac function. Additionally, age-associated hepatic insulin resistance develops in MHC-PPARα mice that may be due to altered cardiac metabolism, functions, and/or inflammatory cytokines." @default.
• W2140799114 created "2016-06-24" @default.
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• W2140799114 date "2005-09-01" @default.
• W2140799114 modified "2023-10-13" @default.
• W2140799114 title "Cardiac-Specific Overexpression of Peroxisome Proliferator–Activated Receptor-α Causes Insulin Resistance in Heart and Liver" @default.
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• W2140799114 doi "https://doi.org/10.2337/diabetes.54.9.2514" @default.
• W2140799114 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16123338" @default.
• W2140799114 hasPublicationYear "2005" @default.
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