A HIGH-FAT DIET INFLUENCES INSULIN-STIMULATED POSTTRANSPORT MUSCLE GLUCOSE-METABOLISM IN RATS

Because of a failure to detect significant quantities of intracellular glucose, it has been generally accepted that transport rather than ph osphorylation is the rate-limiting process of muscle glucose metabolis m under most (but not all) physiological conditions, Here, we have mea sured tissue free levels of the glucose analog 2-deoxy-D-glucose (2DG) in red quadriceps muscle of rats fed a high-fat diet (59% of energy f rom fat) for 3 weeks, to identify the barrier to insulin-stimulated gl ucose uptake previously seen in such animals. Measurements were perfor med on pentobarbital-anesthetized rats following exogenous infusion of radiolabeled 2DG. A glucose clamp was used to maintain plasma insulin at high physiological levels (similar to 120 mU/L). Three other treat ment groups representing normal insulin action (chow-fed), extreme glu cose uptake (maximal insulin stimulation + hyperglycemia), and insulin resistance with elevated free intracellular glucose (epinephrine infu sion) were also studied for comparison. In chow-fed animals, no muscle free 2DG was detected, confirming transport as the rate-limiting proc ess. In fat-fed animals, a significant elevation in muscle free 2DG wa s observed (P<.01 v chow-fed controls), The elevation was similar in m agnitude to that in epinephrine-infused rats, and implied a limitation of insulin action at a posttransport step. This result was confirmed with a more complex modeling analysis. We conclude that posttransport steps influence insulin-stimulated in vivo muscle glucose metabolism i n long-term high-fat-fed rats. Copyright (C) 1997 by W.B. Saunders Com pany.