Intense exercise has unique effects on both insulin release and its roles in glucoregulation: implications for diabetes.

In intense exercise (>80% VO(2max)), unlike at lesser intensities, glucose is the exclusive muscle fuel. It must be mobilized from muscle and liver glycogen in both the fed and fasted states. Therefore, regulation of glucose production (GP) and glucose utilization (GU) have to be different from exercise at <60% VO(2max), in which it is established that the portal glucagon-to-insulin ratio causes the less than or equal to twofold increase in GP. GU is subject to complex regulation by insulin, plasma glucose, alternate substrates, other humoral factors, and muscle factors. At lower intensities, plasma glucose is constant during postabsorptive exercise and declines during postprandial exercise (and often in persons with diabetes). During such exercise, insulin secretion is inhibited by beta-cell alpha-adrenergic receptor activation. In contrast, in intense exercise, GP rises seven- to eightfold and GU rises three- to fourfold; therefore, glycemia increases and plasma insulin decreases minimally, if at all. Indeed, even an increase in insulin during alpha-blockade or during a pancreatic clamp does not prevent this response, nor does pre-exercise hyperinsulinemia due to a prior meal or glucose infusion. At exhaustion, GU initially decreases more than GP, which leads to greater hyperglycemia, requiring a substantial rise in insulin for 40--60 min to restore pre-exercise levels. Absence of this response in type 1 diabetes leads to sustained hyperglycemia, and mimicking it by intravenous infusion restores the normal response. Compelling evidence supports the conclusion that the marked catecholamine responses to intense exercise are responsible for both the GP increment (that occurs even during glucose infusion and postprandially) and the restrained increase of GU. These responses are normal in persons with type 1 diabetes, who often report exercise-induced hyperglycemia, and in whom the clinical challenge is to reproduce the recovery period hyperinsulinemia. Intense exercise in type 2 diabetes requires additional study.