The Avian Proglucagon System

Authors: Richards, Mark; McMurtry, John

Submitted to: General and Comparative Endocrinology
Publication Type: Review Article
Publication Acceptance Date: 9/25/2008
Publication Date: 9/1/2009
Citation: Richards, M.P., McMurtry, J.P. 2009. The avian proglucagon system. General and Comparative Endocrinology. 163(1/2):39-46.

Interpretive Summary: Glucagon is a peptide hormone that plays an important counter-regulatory role to insulin by working to raise blood glucose levels in response to nutritional or environmental stress. In mammals, glucagon is encoded by a single gene in the form of a precursor protein (proglucagon) that also contains additional peptide hormones including two glucagon-like peptide hormones (GLP-1 and GLP-2) which have different physiological functions. GLP-1 acts to promote insulin production by the pancreas and thus raise blood glucose. It also acts to suppress appetite and reduce food intake. GLP-2 is thought to act as a growth factor for the intestine and to promote nutrient absorption and assimilation. The actions of glucagon, GLP-1 and GLP-2 are all mediated by specific receptors present in the cell membranes of tissues that respond to these hormones. Collectively, the peptide hormones derived from the proglucagon precursor and the specific receptors constitute the proglucagon system which plays a vital role in regulating glucose metabolism and energy balance. Despite the fact that this system has been widely studied in a variety of animals and in humans, there is relatively little known about the proglucagon system in birds. Because birds, in general, exhibit high blood glucose levels in both the fasted and fed state and a reduced sensitivity to administered insulin, it is important to understand the basis for this difference in glucose metabolism compared to other animals and how the proglucagon system might be involved. Therefore, the goal of this review was to summarize what is currently known about proglucagon, the receptors that bind glucagon, GLP-1 and GLP-2, and the physiological actions of the proglucagon-derived peptide hormones in birds. This information will help scientists better understand how the proglucagon system functions to control blood glucose, metabolism and energy balance in birds and provide useful background information for future investigations that will explore the nature and actions of this important hormonal system in different avian species.

Technical Abstract: Understanding how the proglucagon system functions in maintaining glycemic control and energy balance in birds, as well as defining its specific roles in regulating metabolism, gastrointestinal tract function and food intake requires detailed knowledge of the components that comprise this system. These include proglucagon, a precursor protein from which glucagon and two glucagon-like peptide hormones (GLP-1 and GLP-2) are derived, and the membrane bound G-protein-coupled receptors that specifically bind glucagon, GLP-1 and GLP-2 to mediate their individual physiological actions. Another key feature of the proglucagon system that is important for regulating its activity in different tissues involves post-translational processing of the proglucagon precursor protein and the individual peptide hormones derived from it. Currently, there is limited information about the proglucagon system in birds with the majority of that coming from studies involving chickens. By summarizing what is currently known about the proglucagon system in birds, this review aims to provide useful background information for future investigations that will explore the nature and actions of this important hormonal system in different avian species.