title: Physiology of proglucagon peptides: role of glucagon and GLP-1 in health and disease.
abstract: 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.
authors.affiliation: Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Darleen A
authors.initials: DA
authors.lastname: Sandoval
authors.affiliation: Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology; D004734:Energy Metabolism; D019858:Enteroendocrine Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D005934:Glucagon / Q000235:genetics / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D005934:Glucagon