Insulin Dose-Response Curves for Stimulation of Splanchnic Glucose Uptake and Suppression of Endogenous Glucose Production Differ in Nondiabetic Humans and Are Abnormal in People With Type 2 Diabetes

To determine whether the insulin dose-response curves for suppression of endogenous glucose production (EGP) and stimulation of splanchnic glucose uptake (SGU) differ in nondiabetic humans and are abnormal in type 2 diabetes, 14 nondiabetic and 12 diabetic subjects were studied. Glucose was clamped at ∼9.5 mmol/l and endogenous hormone secretion inhibited by somatostatin, while glucagon and growth hormone were replaced by an exogenous infusion. Insulin was progressively increased from ∼150 to ∼350 and ∼700 pmol/l by means of an exogenous insulin infusion, while EGP, SGU, and leg glucose uptake (LGU) were measured using the splanchnic and leg catheterization methods, combined with a [3- 3 H]glucose infusion. In nondiabetic subjects, an increase in insulin from ∼150 to ∼350 pmol/l resulted in maximal suppression of EGP, whereas SGU continued to increase ( P P P P P