Sm. Furler et al., A HIGH-FAT DIET INFLUENCES INSULIN-STIMULATED POSTTRANSPORT MUSCLE GLUCOSE-METABOLISM IN RATS, Metabolism, clinical and experimental, 46(9), 1997, pp. 1101-1106
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.