The physiologic action of insulin on glucose uptake and its relevance to the interpretation of the metabolic clearance rate of glucose

Abstract

Glucose uptake (Ru) is dependent upon the concentrations of both glucose and insulin. The metabolic clearance rate of glucose (MCR G), has been used as an in vivo measure of insulin action, because it was said to be independent of the prevailing glucose concentration. The validity of this assumption has recently been challenged. In this study, the effect of insulin concentration on the rate of glucose uptake (Ru) and on the MCR G was studied during euglycemia (5.1 ± 0.3 mmol/L) and moderate hyperglycemia (10.4 ± 0.5 mmol/L) in 17 experiments on nine normal ambulant volunteers. Stable plasma insulin levels were maintained with fixed infusion rates of insulin (0–300 mU/kg/h) and somatostatin (7.5 μg/min). At low insulin concentrations (less than 5 μU/mL) the increase in glucose uptake in response to hyperglycemia was small (5.3 ± 2.3 μmol/kg/min). In contrast, with insulin levels more than 25 μU/mL, there was a steep rise in glucose uptake with hyperglycemia (55 ± 3 μmol/kg/min; range: 44–47 μmol/kg/min). The metabolic clearance rate of glucose fell by an average of 32% with hyperglycemia in the studies at the lowest insulin levels (2.2 ± 0.6 v 1.5 ± 0.1mL/kg/min; 0.15 > P > 0.1). There was no change in the MCR G in the subjects studied at higher insulin levels. It is concluded that (1) low concentrations of insulin are essential for the increase in glucose disposal during hyperglycemia; and (2) provided insulin levels are more than 25 μU/mL and plasma glucose less than 11 mmol/L, MCR G is independent of the plasma glucose concentration and is therefore a valid measure of insulin-mediated glucose uptake.