A study of glucose transport kinetics in man by means of continuous glucose infusions.

Abstract

Continuous glucose infusions were given to 10 healthy subjects, 10 subjects with nonketotic diabetes of varying severity and four ketosis-prone diabetic subjects. The diabetic subjects were treated with insulin so that the fasting blood glucose level at the beginning of their tests would be within or near the normal range. The infusions were continued until a constant blood glucose level was reached. At equilibrium the rate of glucose uptake by the tissues was presumed to be equal to the glucose infusion rate minus the rate of glucose loss in the urine. The rate of glucose uptake at equilibrium was plotted against the increment in the blood glucose concentration produced by the infusion. The rate-concentration relationship for each group of subjects conformed to a hyperbola which fits the Michaelis-Menten equation. This is consistent with the presence throughout the body of saturable cell-membrane glucose transport systems. The values calculated for maximal transport velocity (V) were 59, 22 and 5 g/hr/m2 and for the blood glucose increment at half-maximal velocity (Km) were 62, 152 and 133 mg/100 ml in the healthy and in the nonketotic and ketosis-prone diabetic subjects, respectively. Serum insulin levels during the glucose infusions rose less in the diabetic than in the healthy subjects and did not correlate significantly with the infusion rate. The results suggest that disorders of cellular glucose transport in diabetes can be studied in man; that the abnormality of glucose transport persists in diabetic subjects carefully treated with depot insulin; that glucose transport kinetics are quantitatively similar in nonketotic diabetes of varying clinical severity; and that during prolonged glucose infusions the ratelimiting factor for insulin activity may be the capacity of the islet cells to synthesize new insulin.