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 and glucagon in the regulation of glucose production and gluconeogenesis during a 2-h mild intensity exercise (40% Vo(2)max) in 14 h fasted healthy male subjects. Endogenous insulin and glucagon secretions were suppressed by the infusion of somatostatin. The pancreatic hormones were replaced singly or in combination to match the hormonal concentrations 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 glucose. Hepatic glucose production significantly increased from a resting rate of 12.1 +/- 0.2 to 27.6 +/- 1.4 mu mol . kg(-1). min(-1) during exercise (p < 0.05). In the absence of glucagon, this increase in hepatic glucose production during exercise was totally abolished (p < 0.05). When insulin was made deficient, in the presence of glucagon, there was an overshoot in the increase in hepatic glucose production during exercise 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 when both insulin and glucagon were replaced. Exercise increased gluconeogenesis by 47% above the resting level (p < 0.05). When glucagon was made deficient in the absence or presence of insulin, this increase in gluconeogenesis was totally suppressed (p < 0.05). Furthermore, glucagon 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 mild intensity exercise in healthy subjects, the rise in glucagon is essential for the increase in hepatic glucose production and the increase in gluconeogenesis. It is also suggested that the lower level of insulin during exercise still exerts a restraining effect on glucagon-stimulated glucose production and gluconeogenesis, thus preventing hyperglycemia.