Rats fed a high-fat diet develop skeletal muscle insulin resistance. There is disagreement regarding whether a decrease in the GLUT4 isoform of the glucose transporter is responsible. We found that feeding rats a high-fat diet that reduced the responsiveness of glucose transport to insulin in skeletal muscles by ∼25–45% in 4 weeks, had no significant effect on muscle GLUT4 content. There is also controversy regarding whether the contraction/anoxia activated pathway of glucose transport stimulation is affected by fat feeding. We found that stimulation of muscle glucose transport by either swimming, in situ contractions, or anoxia was depressed to a similar extent as insulin responsiveness in high-fat–fed rats. It has been suggested that the muscle insulin resistance caused by a high-fat diet is due to increased fat oxidation and glucose-fatty acid cycle activity. However, we found that insulin-stimulated glucose transport was reduced by ∼40% when muscles of fat-fed rats were incubated under anoxic conditions under which fatty acid oxidation should not occur. Rats maintained on the high-fat diet up to 32 weeks developed the characteristics of the abdominal obesity syndrome, including insulin resistance, hyperinsulinemia, hyperglycemia, elevated LDL cholesterol and VLDL triglycerides, and marked visceral obesity. We conclude that 1) in rats fed a high-fat diet the muscle insulin resistance is not due to a decrease in total GLUT4 content or to increased fat oxidation, 2) fat feeding also results in resistance of muscle glucose transport to stimulation via the contraction/anoxia pathway, and 3) rats fed a high-fat diet may be a useful model of the abdominal obesity syndrome.
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Original Articles|
November 01 1997
Insulin Resistance of Muscle Glucose Transport in Rats Fed a High-Fat Diet: A Reevaluation
Dong-Ho Han;
Dong-Ho Han
Division of Geriatrics and Gerontology, Department of Medicine, Washington University School of Medicine
St. Louis, Missouri
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Polly A Hansen;
Polly A Hansen
Division of Geriatrics and Gerontology, Department of Medicine, Washington University School of Medicine
St. Louis, Missouri
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Helen H Host;
Helen H Host
Division of Geriatrics and Gerontology, Department of Medicine, Washington University School of Medicine
St. Louis, Missouri
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John O Holloszy
John O Holloszy
Division of Geriatrics and Gerontology, Department of Medicine, Washington University School of Medicine
St. Louis, Missouri
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Address correspondence and reprint requests to John O. Holloszy, MD, Washington University School of Medicine, Division of Geriatrics and Gerontology, 4566 Scott Ave., Campus Box 8113, St. Louis, MO 63110.
Diabetes 1997;46(11):1761–1767
Article history
Received:
January 21 1997
Revision Received:
July 02 1997
Accepted:
July 02 1997
PubMed:
9356023
Citation
Dong-Ho Han, Polly A Hansen, Helen H Host, John O Holloszy; Insulin Resistance of Muscle Glucose Transport in Rats Fed a High-Fat Diet: A Reevaluation. Diabetes 1 November 1997; 46 (11): 1761–1767. https://doi.org/10.2337/diab.46.11.1761
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