Abstract
Glucagon, a hormone secreted by pancreatic alpha cells, contributes to the maintenance of normal blood glucose concentration by inducing hepatic glucose production in response to declining blood glucose. However, glucagon hypersecretion contributes to the pathogenesis of type 2 diabetes. Moreover, diabetes is associated with relative glucagon undersecretion at low blood glucose and oversecretion at normal and high blood glucose. The mechanisms of such alpha cell dysfunctions are not well understood. This article reviews the genesis of alpha cell dysfunctions during the pathogenesis of type 2 diabetes and after the onset of type 1 and type 2 diabetes. It unravels a signaling pathway that contributes to glucose- or hydrogen peroxide-induced glucagon secretion, whose overstimulation contributes to glucagon dysregulation, partly through oxidative stress and reduced ATP synthesis. The signaling pathway involves phosphatidylinositol-3-kinase, protein kinase B, protein kinase C delta, non-receptor tyrosine kinase Src, and phospholipase C gamma-1. This knowledge will be useful in the design of new antidiabetic agents or regimens.
Highlights
The hormone glucagon, produced by pancreatic alpha cells, contributes to the regulation of blood glucose by promoting hepatic glucose production in response to declining blood glucose
A hormone secreted by pancreatic alpha cells, contributes to the maintenance of normal blood glucose concentration by inducing hepatic glucose production in response to declining blood glucose
It unravels a signaling pathway that contributes to glucose- or hydrogen peroxide-induced glucagon secretion, whose overstimulation contributes to glucagon dysregulation, partly through oxidative stress and reduced ATP synthesis
Summary
The hormone glucagon, produced by pancreatic alpha cells, contributes to the regulation of blood glucose by promoting hepatic glucose production in response to declining blood glucose. Its excessive secretion contributes to the development of type 2 diabetes [1, 2] In both type 1 and type 2 diabetes, its secretion is dysregulated; with hypersecretion at moderate and high glucose, aggravating hyperglycemia; and failure of secretion at low glucose, leading to life-threatening hypoglycemia [2, 3]. The mechanisms of such alpha cell dysregulations are not well understood. A synthesis of the literature unveils a signaling pathway that contributes to glucose- and/or hydrogen peroxide-induced glucagon secretion Excessive activation of this pathway in diabetes dysregulates glucagon secretion through alpha cell oxidative stress and reduced ATP synthesis. The relevance of such a pathway to the antihyperglycemic and antihypoglycemic effects of some antidiabetic agents is discussed
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
