Insulin as a physiological modulator of glucagon secretion
Open Access
- 1 October 2008
- journal article
- review article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 295 (4), E751-E761
- https://doi.org/10.1152/ajpendo.90295.2008
Abstract
Glucose homeostasis is regulated primarily by the opposing actions of insulin and glucagon, hormones that are secreted by pancreatic islets from β-cells and α-cells, respectively. Insulin secretion is increased in response to elevated blood glucose to maintain normoglycemia by stimulating glucose transport in muscle and adipocytes and reducing glucose production by inhibiting gluconeogenesis in the liver. Whereas glucagon secretion is suppressed by hyperglycemia, it is stimulated during hypoglycemia, promoting hepatic glucose production and ultimately raising blood glucose levels. Diabetic hyperglycemia occurs as the result of insufficient insulin secretion from the β-cells and/or lack of insulin action due to peripheral insulin resistance. Remarkably, excessive secretion of glucagon from the α-cells is also a major contributor to the development of diabetic hyperglycemia. Insulin is a physiological suppressor of glucagon secretion; however, at the cellular and molecular levels, how intraislet insulin exerts its suppressive effect on the α-cells is not very clear. Although the inhibitory effect of insulin on glucagon gene expression is an important means to regulate glucagon secretion, recent studies suggest that the underlying mechanisms of the intraislet insulin on suppression of glucagon secretion involve the modulation of KATP channel activity and the activation of the GABA-GABAA receptor system. Nevertheless, regulation of glucagon secretion is multifactorial and yet to be fully understood.Keywords
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