Whole Body Glucose Metabolism in Experimental Insulin-Dependent Diabetes after Initiation or Termination of Insulin Administration*)

Abstract

To investigate the kinetics in glucose metabolism, diabetic dogs were infused with double labelled glucose either when they were connected to an artificial beta cell after overnight insulin withdrawal (study I) or when they were disconnected from insulin supply after excellent metabolic control (study II). Fourteen hours after the last insulin injection, the animals had three-fold elevated rates of appearance Ra and of disappearance Rd of glucose in relation to non-diabetic controls; the metabolic clearance rate was reduced, glucose carbon recirculation was slightly elevated, and the % lactate from glucose was not altered. Glucosuria contributed approximately 30% to the elevated glucose turnover. In study I, Ra was normalized within 45 min after insulin supply but Rd increased transiently before returning to normal. In study II, plasma insulin was zero 30 min after termination of insulin supply. Ra increased immediately; Rd decreased slightly but increased thereafter. Lactate was elevated under all conditions. Its production from glucose increased slightly after initiation of insulin action. Glucose carbon recirculation was reduced to subnormal values when the animals were euglycemic but hyperinsulinemic.--It is concluded that even short intervals of relative lack of insulin action followed by restoration of glucose homeostasis, may induce wasting of substrates.