Nonhypoglycemic glucoregulation: role of glycerol and glucoregulatory hormones

Abstract

The contribution of glycerol to the increased glucose formation was determined and the release of possible glucoregulatory hormones during an increased removal of glucose from the circulation was examined. In dogs in the postabsorptive (PA) or fasted state, the rate of release of glucose and glycerol into the circulation was calculated by tracer methods before, during and after the infusion of phlorizin. The incorporation of 14C atoms from glycerol into glucose and lactate was also followed. Plasma concentrations of glucagon, insulin, catecholamines, cortisol and ACTH were monitored. During the infusion of phlorizin in the PA state, an increase in glucose production nearly compensated for the urinary loss; glycerol release was increased transiently, but the fraction of utilized glycerol converted to glucose remained unchanged; plasma glucagon doubled but insulin and dopamine decreased; the level of the other hormones remained unchanged; and there was no change in plasma lactate or the incorporation of label from glycerol into lactate. In the fasted state, glucose production increased; nevertheless, plasma glucose fell by 25 mg/dl; glycerol release was significantly raised; a larger fraction of utilized glycerol was converted to glucose; plasma glucagon, ACTH and cortisol but not catecholamines increased, while plasma insulin decreased; a larger fraction of plasma lactate arose from glycerol. In conclusion, in nonhypoglycemic glucoregulation, glycerol contributes only to a minor extent to the increment in hepatic glucose production; glucagon but not catecholamines are released in both PA and fasted states; ACTH and cortisol are released only in fasted dogs, presumably in response to neuroglucopenia; in fasted dogs the plasma concentration of ACTH and cortisol but not catecholamines increased, suggesting that the former response is more sensitive to a decrease in plasma glucose; and in fasted dogs glycerol is a substrate more of oxidation than gluconeogenesis.