Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats

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Abstract
The euglycemic hyperinsulinemic clamp technique in conscious unrestrained rats was used to examine the effect of insulin on glucose metabolism in metabolically distinct skeletal muscle in vivo. Tissue glucose metabolic rate (R''g) was estimated using 2-[3H]deoxyglucose, and glucose disposal was examined by measuring glycogen content and [14C]glucose incoporation into glycogen in 4 different muscles. Insulin sensitivity varied among different muscle types in that the insulin concentration required for half-maximal stimulation of R''g was 80, 150, 280 and 20 mU/l for soleus (SOL), red gastrocnemius (RG), white gastrocnemius (WG) and extensor digitorum longus, respectively. There were similar relative differences in the maximal effect of insulin on R''g in these in these muscles. Maximal insulin stimulation almost doubled muscle glycogen content in RG and SOL, whereas there was no change in WG. The relationship between R''g and glycogen synthesis indicated that increased glucose uptake resulted predominantly in glycogen storage. There was an excellent relationship between maximal R''g and blood flow in different muscles. There is marked heterogeneity in insulin sensitivity and responsiveness among muscles of different fiber composition. Insulin-induced increased increases in total peripheral glucose disposal occur predominantly in muscles containing a high proportion of oxidative fibers. Therefore the relative proportion of oxidation to glycolytic muscle fibers may be important factors in determining whole body insulin sensitivity.

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