Exercise-induced hepatic glucose output is precisely sensitive to the rate of systemic glucose supply

Abstract

It has previously been established that a glucose infusion causing hyperglycemia and alterations in the levels of glucoregulatory hormones suppresses the exercise-induced increment in systemic glucose appearance (R a). In an attempt to define the mechanisms responsible for this suppression of R a, five normal subjects were exercised for 60 minutes on a bicycle ergometer at 60% V̇o 2 max on two occasions. On both occasions R a was measured by a nonsteady state technique using a constant infusion of 3- 3H-glucose. On the second occasion, an IV infusion of glucose was administered in a stepwise fashion to simulate in timing and magnitude the measured R a response from the first study. Endogenous glucose production in the second study, estimated by subtracting the amount of glucose infused from the measured R a response, did not increase above basal ( endogenous glucose output response = 0.5 ± 8.4 mmol 60 min v control study 60.2 ± 6.6 mmol 60 min , P < 0.01 ). The suppression of R a was associated with a small but significant effect on venous plasma glucose (increment above basal less than 0.3 mmol/L, P < 0.05) and a significant change in glucose metabolic clearance rate during the second 30 minutes of exercise. Serum insulin, C-peptide, cortisol, growth hormone, and plasma glucagon responses to exercise were not significantly affected by glucose infusion and the ratio of circulating insulin to glucagon was also not affected. These results indicate that hepatic glucose output during exercise is precisely sensitive to glucose supply. The feedback inhibition is presumably mediated by a small increase in plasma glucose but cannot readily be accounted for by changes in glucoregulatory hormones. A direct or indirect non hormonal feedback effect of blood glucose on hepatic glucose output is suggested.