Regulation of glucose fluxes during exercise in the postabsorptive state.

The increase in glucose utilization by the working muscle would lead to hypoglycemia were it not accompanied by an increase in hepatic glucose production. Although the increase in glucose uptake is normally driven by mechanisms that are primarily independent of the action of insulin and other hormones, the response of the liver appears to be closely controlled by the endocrine system. Although considerable progress has been made in understanding the bases for the increases in glucose utilization and production, the means by which these two processes are coordinated to form the exercise response are unclear (e.g. feedback or central feedforward control). Work intensity affects the mechanisms by which glucose fluxes are regulated. For example, during moderate-intensity exercise, the glucoregulatory response resembles glucoregulation in the basal state in that under both conditions, glucose release from the liver is controlled by glucagon and insulin, and blood glucose levels are tightly controlled. The response to high-intensity exercise, on the other hand, takes on characteristics of the stress response, as described by Cannon (13). That is, the catecholamine response increases disproportionately for a given increment in work intensity, and glucose levels are no longer closely regulated, but increase. The specific factors that turn exercise into stress at higher work intensities are not well defined. Determining factors involved in the regulation of glucose fluxes are limited in some respects because the body is more sensitive than are experimental detection methods to various stimuli (glucose, hormones, neurotransmitter release). More complete delineation of mechanisms involved in the regulation of glucose fluxes will require the development of improved techniques and unique experimental models. The trend in the physiological sciences is for more study at the level of the gene. Technical limitations will be overcome or circumvented as knowledge of gene regulation and the development of genetically engineered animal models provide new avenues with which to address basic questions regarding the control of glucose fluxes during exercise.