Physiology of proglucagon peptides: role of glucagon and GLP-1 in health and disease.

Published

Journal Article (Review)

The preproglucagon gene (Gcg) is expressed by specific enteroendocrine cells (L-cells) of the intestinal mucosa, pancreatic islet α-cells, and a discrete set of neurons within the nucleus of the solitary tract. Gcg encodes multiple peptides including glucagon, glucagon-like peptide-1, glucagon-like peptide-2, oxyntomodulin, and glicentin. Of these, glucagon and GLP-1 have received the most attention because of important roles in glucose metabolism, involvement in diabetes and other disorders, and application to therapeutics. The generally accepted model is that GLP-1 improves glucose homeostasis indirectly via stimulation of nutrient-induced insulin release and by reducing glucagon secretion. Yet the body of literature surrounding GLP-1 physiology reveals an incompletely understood and complex system that includes peripheral and central GLP-1 actions to regulate energy and glucose homeostasis. On the other hand, glucagon is established principally as a counterregulatory hormone, increasing in response to physiological challenges that threaten adequate blood glucose levels and driving glucose production to restore euglycemia. However, there also exists a potential role for glucagon in regulating energy expenditure that has recently been suggested in pharmacological studies. It is also becoming apparent that there is cross-talk between the proglucagon derived-peptides, e.g., GLP-1 inhibits glucagon secretion, and some additive or synergistic pharmacological interaction between GLP-1 and glucagon, e.g., dual glucagon/GLP-1 agonists cause more weight loss than single agonists. In this review, we discuss the physiological functions of both glucagon and GLP-1 by comparing and contrasting how these peptides function, variably in concert and opposition, to regulate glucose and energy homeostasis.

Full Text

Duke Authors

Cited Authors

  • Sandoval, DA; D'Alessio, DA

Published Date

  • April 2015

Published In

Volume / Issue

  • 95 / 2

Start / End Page

  • 513 - 548

PubMed ID

  • 25834231

Pubmed Central ID

  • 25834231

Electronic International Standard Serial Number (EISSN)

  • 1522-1210

International Standard Serial Number (ISSN)

  • 0031-9333

Digital Object Identifier (DOI)

  • 10.1152/physrev.00013.2014

Language

  • eng