AJP - Endocrinology and Metabolism, Vol 259, Issue 4 E517-E523, Copyright © 1990 by American Physiological Society
Insulin binding to individual rat skeletal muscles
D. J. Koerker, I. R. Sweet and D. G. Baskin
Department of Medicine, University of Washington, Seattle 98195.
Studies of insulin binding to skeletal muscle, performed using sarcolemmal
membrane preparations or whole muscle incubations of mixed muscle or
typical red (soleus, psoas) or white [extensor digitorum longus (EDL),
gastrocnemius] muscle, have suggested that red muscle binds more insulin
than white muscle. We have evaluated this hypothesis using cryostat
sections of unfixed tissue to measure insulin binding in a broad range of
skeletal muscles; many were of similar fiber-type profiles. Insulin binding
per square millimeter of skeletal muscle slice was measured by
autoradiography and computer-assisted densitometry. We found a 4.5-fold
range in specific insulin tracer binding, with heart and predominantly
slow-twitch oxidative muscles (SO) at the high end and the predominantly
fast-twitch glycolytic (FG) muscles at the low end of the range. This
pattern reflects insulin sensitivity. Evaluation of displacement curves for
insulin binding yielded linear Scatchard plots. The dissociation constants
varied over a ninefold range (0.26-2.06 nM). Binding capacity varied from
12.2 to 82.7 fmol/mm2. Neither binding parameter was correlated with fiber
type or insulin sensitivity; e.g., among three muscles of similar
fiber-type profile, the EDL had high numbers of low-affinity binding sites,
whereas the quadriceps had low numbers of high-affinity sites. In summary,
considerable heterogeneity in insulin binding was found among hindlimb
muscles of the rat, which can be attributed to heterogeneity in binding
affinities and the numbers of binding sites. It can be concluded that a
given fiber type is not uniquely associated with a set of insulin binding
parameters that result in high or low binding.
