The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog.

Abstract

A B S T R A C T The aim of the present experiments was to determine the role of insulin and glucagon in the regulation of basal glucose production in dogs fasted overnight. A deficiency of either or both pancreatic hormones was achieved by infusing somatostatin (1 ug/kg per min), a potent inhibitor of both insulin and glucagon secretion, alone or in combination with intraportal replacement infusions of either pancreatic hormone. Infusion of somatostatin alone caused the arterial levels of insulin and glucagon to drop rapidly by 72+6 and 81±8%, respectively. Intraportal infusion of insulin and glucagon at rates of400 ,uU/kg per min and 1 ng/kg per min, respectively, resulted in the maintenance of the basal levels of each hormone. Glucose production was measured using tracer (primed constant infusion of [3-3H]glucose) and arteriovenous difference techniques.Isolated glucagon deficiency resulted in a 35+5% (P < 0.05) rapid and sustained decrease in glucose production which was abolished upon restoration ofthe plasma glucagon level. Isolated insulin deficiency resulted in a 52+16% (P < 0.01) increase in the rate of glucose production which was abolished when the insulin level was restored. Somatostatin had no effect on glucose production when the changes in the pancreatic hormone levels which it normally induces were prevented by simultaneous intraportal infusion of both insulin and glucagon.In conclusion, in the anesthetized dog fasted overThis work was presented in part at

Leptin increases circulating glucose, insulin and glucagon via sympathetic neural activation in fasted mice

“…30 It is possible that the leptininduced increase of plasma insulin observed in the present study occurs as an indirect response to sympathetic activation, perhaps in conjunction with adrenaline released from the adrenal medulla. 32,33 This would stimulate glucagon secretion and increase hepatic glucose production, 35 resulting in increased circulating glucose and glucagon, which in turn stimulate insulin secretion.…”

Beneficial effects of intercellular interactions between pancreatic islet cells in blood glucose regulation

“…Although the endogenous strengths of the interactions from δ-cells to α-and β-cells are not known, the exogenous stimulus of somatostatin has been reported to inhibit both insulin and glucagon secretion to a similar degree (Cherrington et al, 1976).…”

“…The minimal basal secretion of glucagon compensates the glucose uptake in the liver while basal secretion of insulin inhibits over-secretion of the basal glucagon (Cherrington et al, 1976).…”

“…In contrast, insulin, secreted by β-cells, inhibits glucagon secretion of α-cells (Cherrington et al, 1976;Franklin et al, 2005;Ravier & Rutter, 2005;Samols & Harrison, 1976;Soria et al, 2000), which appears natural. Furthermore, the role of the third cell-type, δ-cells, is still not completely known although there have been reports that somatostatin hormone, secreted by δ-cells, suppresses the hormone secretion of both α-and β-cells (Cherrington et al, 1976;Daunt et al, 2006;Orci & Unger, 1975;Soria et al, 2000).…”

“…The importance of this bi-hormonal mechanism for glucose homeostasis has been well recognized (Cherrington et al, 1976). However, it should be noted that endocrine cells in the islet interact with each other rather than act independently.…”