T he counterregulatory response to insulininduced hypoglycemia in vivo consists of an increase in glucagon secretion and a decrease in insulin release, in addition to changes in the plasma levels of other hormones and metabolites. However, insulin is known to inhibit its own release and to reduce glucagon secretion. Therefore, it has been difficult to separate the effects of hypoglycemia per se from those of combined hyperinsulinemia and hypoglycemia on insulin and glucagon secretion.A recent study made use of a glycogen phosphorylase inhibitor to create mild hypoglycemia in the conscious dog by reducing glucose production, thereby avoiding the confounding affects of hyperinsulinemia (1). In that study, a change in glycemia of only 0.6 mmol/l (5.8 Ϯ 0.2 to 5.2 Ϯ 0.3 mmol/l by 30 min) resulted in a significant fall in plasma insulin and a significant rise in plasma glucagon. A glucose level of 5.2 mmol/l is much higher than the traditional threshold of 3.8 mmol/l generally thought to be required for the ␣-cell response to insulin-induced hypoglycemia in humans (2) and dogs (3). It thus seems that the ␣-cell is more sensitive to a decline in glucose than previously thought. The -cell, however, has already been shown to respond to small changes in glucose during insulin-induced hypoglycemia. Specifically, plasma c-peptide levels, an index of insulin secretion, fell as glucose decreased from 5.1 to 4.9 or from 4.7 to 4.4 mmol (4,5). Our previous data obtained using the glycogen phosphorylase inhibitor showed that the -cell also responds sensitively to hypoglycemia in the absence of exogenous insulin administration (1).The exact mechanism by which insulin secretion is controlled in response to hypoglycemia is controversial. Although insulin secretion in vivo seems to be very sensitive to small changes in glucose, work in isolated rodent islets has shown that insulin secretion does not change when the glucose concentration falls from ϳ4.5 to 0 mmol/l (6,7). This could mean that insulin secretion had already been maximally inhibited at a glucose level in the 4 -5 mmol/l range. This is conceivable, especially because the threshold for a decrease in insulin secretion in rodent islets is most likely higher than for canine islets, as a result of the increased fasting plasma glucose level in rodents. However, this failure of a small fall in glucose to inhibit insulin could also mean that some factor, such as an intact nervous system or an intact circulatory system, allows for the sensitive control of the -cell in vivo and that this control is lost in vitro. In support of neural regulation, epinephrine (released from the adrenal medulla in response to sympathetic nerve stimulation) and norepinephrine (the classical sympathetic nervous system [SNS] neurotransmitter) both have been shown to increase during hypoglycemia and to inhibit insulin secretion both in vitro and in vivo (8 -10). Additional evidence to suggest that the SNS can control -cell insulin release is that direct stimulation of sympathetic nerves results in a...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.