Alpha- and beta-cell interrelationships in health and disease

The variations in secretory responses of the pancreatic alpha and beta cells in response to variations in nutrient supply and demand in health and disease are demonstrated. The biologic capability of insulin and glucagon to control on a moment-to-moment basis the disposition of exogenous and endogenous fuels is considered. An appropriate insulin-glucagon response ensures the most efficient storage of ingested nutrients, while maintaining fuel requirements from endogenous sources when food is not available. The glucose supply, both present and past, seems to influence the insulin-glucagon response to all other nutrients, to hormones, and to neural influences more than any other factor. The intracellular entry and metabolism of glucose appears to be required to suppress alpha cell secretion below the basal level and to prevent its hyperresponsiveness to various stimuli. An inappropriately low concentration of insulin and/or high level of glucagon relative to fuel availability is observed in genetic diabetes, and in a variety of stressful illnesses such as severe infection, trauma, burns, fetal distress, and other conditions, all of which are characterized by a negative nitrogen balance. The use of amino acids to produce glucose and urea at the expense of protein synthesis is presumably promoted by a low insulin: glucagon ratio and may be a factor in the catabolic manifestations of these diseases.