HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/E751    most recent 90295.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Bansal, P. Articles by Wang, Q. Search for Related Content PubMed PubMed Citation Articles by Bansal, P. Articles by Wang, Q.

REVIEWS

Insulin as a physiological modulator of glucagon secretion

¹Department of Physiology, ²Department of Medicine, and ³Division of Endocrinology and Metabolism, Li Ka-Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada

Submitted 15 March 2008 ; accepted in final form 15 July 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 -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 -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 -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 K_ATP channel activity and the activation of the GABA-GABA_A receptor system. Nevertheless, regulation of glucagon secretion is multifactorial and yet to be fully understood.

diabetes; hyperglycemia; -aminobutyric acid; adenosine 5'-triphosphate-sensitive K⁺ channel

This article has been cited by other articles:

				S. Ali and D. J. Drucker Benefits and limitations of reducing glucagon action for the treatment of type 2 diabetes Am J Physiol Endocrinol Metab, March 1, 2009; 296(3): E415 - E421. [Abstract] [Full Text] [PDF]