Time Dependence of Insulin Action in Muscle and Adipose Tissue in the Rat In Vivo: An Increasing Response in Adipose Tissue with Time

The relative time dependency of enhancement of glucose metabolism by insulin in individual tissues has not been examined previously in vivo. Using the glucose clamp technique in the rat combined with radiolabeled 2-deoxyglucose (³H or ¹⁴C-2DG) administration, we have estimated a glucose metabolic index (Rg') in major insulin-sensitive tissues at two different times (between 40–55 min and 80–95 min) after onset of hyperinsulinemia (insulin levels of approximately 130 mU/L). At the completion of the clamp (125 min), eight different skeletal muscles and three different adipose tissue beds were rapidly removed for estimation of Rg', based on the accumulation of intracellular tracer 2DG-6-phosphate (2DGP). Insulin-stimulated Rg' was 60–70% higher at 80–95 min than at 40–55 min after elevation of insulin levels in all three adipose tissue beds (P < 0.01). In contrast, insulin-stimulated whole body glucose utilization and Rg' in all skeletal muscles were not significantly different at these two times. The constancy of insulin action in skeletal muscles during the 2-h euglycemic clamp, as determined in these studies, does not support the concept that the glucose clamp represents an integral of many rapidly changing individual tissue responses. In conclusion, while the amount of insulin-stimulated glucose uptake in adipose tissue is low compared with muscle, the fraction increases with duration of insulin elevation. This effect may have significant implications in hyperinsulinemic States.