The role of glucagon in the pathophysiology and management of diabetes

Georgia R. Kulina, Elliot J. Rayfield

Research output: Contribution to journalReview articlepeer-review

29 Scopus citations


Objective: There is general recognition that insulin and glucagon are the main hormones involved in the pathophysiology of diabetes, but the role of glucagon in diabetes is complex and in some circumstances controversial. The increasing appreciation of the role of glucagon in currently used hypoglycemic agents and the ongoing development of glucagon-targeted therapies underscores glucagon's important contribution in optimizing diabetes management. The current review provides a background on glucagon physiology and pathophysiology and an update for investigators, endocrinologists, and other healthcare providers on glucagon-modulating therapies. Methods: A literature review was conducted utilizing published literature in PubMed and AccessMedicine including the years 1922-2015 using the following key words: glucagon, bihormonal, diabetes mellitus, glucagon antagonists, glucagon-targeted therapies. Results: Glucagon is a counterregulatory hormone that promotes hepatic glucose production, thus preventing hypoglycemia in normal physiology. In patients with diabetes mellitus, glucagon secretion may be unregulated, which contributes to problems with glucose homeostasis. Several of the most effective therapies for diabetes have been found to suppress glucagon secretion or action, which may contribute to their success. Additionally, glucagon-specific targeted therapies, such as glucagon receptor antagonists, are being studied at a basic and clinical level. Conclusion: Glucagon plays an important role in contributing to hyperglycemia in patients with diabetes. Utilizing hypoglycemic agents that decrease glucagon secretion or inhibit glucagon action can help improve glycemic control, making these agents a valuable resource in diabetes therapy.

Original languageEnglish
Pages (from-to)612-621
Number of pages10
JournalEndocrine Practice
Issue number5
StatePublished - 2016


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