The Influence of Graded Hyperglycemia with and without Physiological Hyperinsulinemia on Forearm Glucose Uptake and Other Metabolic Responses in Man

We studied the influence of hyperglycemia on glucose homeostasis in man by determining the effect of graded hyperglycemia on peripheral glucose uptake and systemic metabolism in the presence of basal and increased serum insulin concentrations in 10 normal men. This was achieved by the simultaneous application of forearm and clamp techniques (euglycemic and hyperglycemic) during the combined iv infusion of somatostatin, glucagon, and insulin. While mean (±SE) basal serum insulin levels (14 ± 2 µU/ml) were maintained, the elevation of fasting arterial glucose concentrations (90 ± 1 mg/dl) to 146 ± 1 and 202 ± 1 mg/dl (each for 120 min) increased forearm glucose uptake (FGU) only modestly from 0.06 ± 0.01 to 0.15 ± 0.02 and then to 0.24 ± 0.03 mg/100 ml forearm-min, respectively. During physiological hyperinsulinemia (47 ± 3 µU/ml), the influence of similar graded hyperglycemia on FGU was considerably enhanced. At plasma glucose concentrations of 90 ± 1, 139 ± 1, and 206 ± 1 mg/dl, FGU rose to 0.33 ± 0.05, 0...