The role of glucose, insulin and glucagon in the regulation of food intake and body weight.

Glucose and related pancreatic hormones play a major role in the metabolism of monogastric mammals yet their influence on hunger and/or satiety is, as yet, poorly understood. Glucose, insulin and glucagon rise during a meal and gradually decline to baseline levels shortly after a meal. A sudden drop in plasma glucose as well as insulin have been reported just prior to the onset of a meal but the functional significance of this is not yet clear. Systemic injections of glucose have no acute satiety effects but intraduodenal and intrahepatic infusions reduce food intake and free-feeding and deprived animals respectively. Treatments which decrease cellular glucose utilization directly (2-DG) or indirectly (insulin) increase food intake while exogenous glucagon (which produces hyperglycemia) decreases it. There is considerable evidence that some or all of these effects may be due to a direct central action of glucose, 2-DG, insulin, and glucagon on brain mechanisms concerned with the regulation of hunger and satiety although influences on peripheral "glucoreceptors" have been demonstrated as well. The functional significance of glucoprivic feeding is, however, questioned. The feeding response to 2-DG and related compounds is capricious, and its temporal course does not parallel the hyperglycemic reaction which presumably reflects cellular glucopenia. Moreover, numerous brain lesions which increase, decrease, or have no effect on ad lib intake and often have no effect on the response to deprivation have been shown to severely impair or abolish feeding responses to systemic injections of 2-DG that produce severe central as well as peripheral glucopenia. Feeding responses to insulin are intact after most of these lesions, suggesting that this hormone may influence food intake in a fundamentally different fashion. The mechanism of insulin action is not understood--the classic feeding response is obtained only with doses that are pharmacological when compared to normal plasma levels and there is increasing evidence that lower doses may have opposite, inhibitory effects on food intake and body weight. Relatively small doses of glucagon decrease food intake (although opposite facilitatory effects have been reported after even smaller doses) but the effect does not appear to be due to hepatic mobilization of glucose as initially assumed. Decreases in food intake after intracranial injections of very small doses suggest a direct central action.