Influence of Plasma Glucose and Insulin Concentration on Plasma Glucose Clearance in Man

Abstract

We examined the influence of plasma glucose concentration on whole-body glucose uptake and glucose clearance at two physiologic levels of hyperinsulinemia. Twelve healthy, young volunteers were divided into two groups (A and B); each subject participated in three studies. In group A, plasma insulin was raised and maintained by ∼100 μU/ml for 3 h, while plasma glucose concentration was clamped at hypoglycemic (60 ± 1 mg/dl), euglycemic (89 ± 1 mg/dl), or hyperglycemic (165 ± 3 mg/dl) levels. In group B, plasma insulin was raised by ∼50 μU/ml, while plasma glucose was clamped at 62 ± 1,86 ±2, or 143 ± 3 mg/dl for 3 h. At the higher insulin level (group A), glucose uptake rose from 5.2 ± 0.5 to 7.3 ± 0.6 to 12.2 ±1.0 mg/min· kg as plasma glucose was varied from low to high levels; glucose clearance fell slightly from 8.8 ± 1.0 to 7.8 ± 0.7 to 7.3 ± 0.6 ml/min·kg during the hypo-, eu-, and hyperglycemic clamps (P = NS). At the lower insulin level (group B), glucose uptake rose from 6.0 ± 1.2 to 8.1 ±1.7 mg/min·kg (P < 0.05) with increasing glucose levels, whereas glucose clearance fell significantly (P < 0.01) from 9.7 ± 1.8 to 5.6 ±1.1 ml/min·kg. When the data from both groups were analyzed together, insulin had a stimulatory effect on both glucose uptake and clearance. Elevation of the plasma glucose level had a similar stimulatory effect on glucose uptake (P < 0.001) but inhibited glucose clearance (P < 0.01). This inhibition, however, was modest (14% for the change from hypo- to euglycemia, and 16% for the change from eu- to hyperglycemia). We conclude that physiologic hyperglycemia exerts a modest inhibitory effect on glucose clearance, which is largely overcome at higher, yet still physiologic, plasma insulin levels (∼100 μU/ml).