Dose-response curves for in vivo insulin sensitivity in individual tissues in rats

A technique is described for examining in vivo insulin action on glucose utilization in individual tissues in the intact conscious rat. Indices of tissue glucose metabolic rate Rg' and of the percentage of total glucose uptake incorporated into specific storage products (Cf) are derived from tissue analysis after bolus administration of 2-[3H]deoxyglucose and [14C]glucose during the plateau phase of the euglycemic clamp. The effects of insulin elevation have been examined in several tissues. Rg' in diaphragm increased 10-fold over basal (maximal) with a half-maximal sensitivity (ED50) of 150 mU/l. This was similar to the ED50 for net whole body glucose utilization of 133 mU/l. In adipose tissue Rg' increased by twofold and Cf into lipids by sixfold; both were near maximal at 150 mU/l (ED50 of 60 mU/l). A small but significant insulin effect (Rg' increased 2-fold) was found in lung. Insulin did not significantly increase Cf into total liver lipids or glycogen. The methodology described here significantly increases the usefulness of the glucose clamp technique in the study of insulin action. Dose-response curves for insulin action during the euglycemic clamp vary considerably among different target tissues in the rat.