INSULIN-RESISTANCE OF MUSCLE GLUCOSE-TRANSPORT IN RATS FED A HIGH-FATDIET - A REEVALUATION

Rats fed a high-fat diet develop skeletal muscle insulin resistance. T here 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 similar to 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 stimu lation of muscle glucose transport by either swimming, in situ contrac tions, or anoxia was depressed to a similar extent as insulin responsi veness in high-fat-fed rats. It has been suggested that the muscle ins ulin resistance caused by a high-fat diet is due to increased fat oxid ation and glucose-fatty acid cycle activity. However, we found that in sulin-stimulated glucose transport was reduced by similar to 40% when muscles of fat-fed rats were incubated under anoxic conditions under w hich fatty acid oxidation should not occur. Rats maintained on the hig h-fat diet up to 32 weeks developed the characteristics of the abdomin al obesity syndrome, including insulin resistance, hyperinsulinemia, h yperglycemia, elevated LDL cholesterol and VLDL triglycerides, and mar ked 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 contract ion/anoxia pathway, and 3) rats fed a high-fat diet may be a useful mo del of the abdominal obesity syndrome.