GLUCOSE-METABOLISM DURING EXERCISE IN MAN - THE ROLE OF INSULIN AND GLUCAGON IN THE REGULATION OF HEPATIC GLUCOSE-PRODUCTION AND GLUCONEOGENESIS

This study was designed to further characterize the role of insulin an d glucagon in the regulation of glucose production and gluconeogenesis during a 2-h mild intensity exercise (40% Vo(2)max) in 14 h fasted he althy male subjects. Endogenous insulin and glucagon secretions were s uppressed by the infusion of somatostatin. The pancreatic hormones wer e replaced singly or in combination to match the hormonal concentratio ns observed during exercise in control subjects. Glucose turnover was determined by a tracer method using the stable isotope D-[2,3,4,6,6-H- 2]glucose. Gluconeogenesis was estimated by the simultaneous infusion of L-[1,2,3-C-13]alanine to follow the conversion of alanine to glucos e. Hepatic glucose production significantly increased from a resting r ate of 12.1 +/- 0.2 to 27.6 +/- 1.4 mu mol . kg(-1). min(-1) during ex ercise (p < 0.05). In the absence of glucagon, this increase in hepati c glucose production during exercise was totally abolished (p < 0.05). When insulin was made deficient, in the presence of glucagon, there w as an overshoot in the increase in hepatic glucose production during e xercise to 36.4 +/- 1.6 mu mol . kg(-1). min(-1)(p < 0.05). The normal increase in hepatic glucose output during exercise was reproduced whe n both insulin and glucagon were replaced. Exercise increased gluconeo genesis by 47% above the resting level (p < 0.05). When glucagon was m ade deficient in the absence or presence of insulin, this increase in gluconeogenesis was totally suppressed (p < 0.05). Furthermore, glucag on replacement during exercise in the absence of insulin resulted in a further increase in gluconeogenesis to 93% above resting value (p < 0 .05). From these observations, it is concluded that during prolonged m ild intensity exercise in healthy subjects, the rise in glucagon is es sential for the increase in hepatic glucose production and the increas e in gluconeogenesis. It is also suggested that the lower level of ins ulin during exercise still exerts a restraining effect on glucagon-sti mulated glucose production and gluconeogenesis, thus preventing hyperg lycemia.