Measurement of Glucose Disposal Rates in Normal and Diabetic Human Subjects After Repeated Intravenous Injections of Glucose1

Abstract

In an attempt to elicit maximal insulin release from the pancreas, 3 successive intravenous injections of glucose (each 25 g) were given to each of 38 normal subjects and 15 patients with diabetes mellltus. After allowing for glycosuria, the glucose disposal rate (GDR) after each injection was calculated by multiplying the glucose space by the observed rate of decline of the plasma glucose concentration from 10 to 35 min after each injection. GDR increased significantly after the 2nd and 3rd (cf the first) injection in normal subjects and in patients with diabetes mellltus who could be satisfactorily controlled on tolbutamide, but not in diabetics who required therapy with insulin. The GDR after the initial injection of glucose was highest in the young adult normal subjects, lower in elderly normal subjects (>70 years), lower still in the tolbutamide-responsive diabetics, and lowest in the insulin-dependent diabetics. Blood insulinlike activity, assayed in the rat epididymal fat pad, usually rose higher after the 2nd or 3rd than after the 1st injection in the normal subjects. For this reason, and because the normal pattern of increasing GDR''s could best be mimicked in insulin-dependent diabetics by injecting increasing doses of regular insulin with each load of glucose, it is concluded that the successive injections of glucose probably stimulate progressively increasing release of insulin from the pancreas iIn normal subjects. Tolbutamide administration did not accelerate the glucose disposal rates.