Revisiting the Pharmacological Value of Glucagon: An Editorial for the Special Issue “The Biology and Pharmacology of Glucagon”

Kirk Habegger,Timo D. Müller

doi:10.3390/ijms21020383

Abstract

In 1921, a Canadian research team led by Frederick Banting and John Macleod succeeded in the isolation of insulin from pancreatic homogenate [...].

Highlights

Emerging evidence suggests that beyond its counterregulatory role in glucose homeostasis, glucagon regulates a range of actions including lipolysis, ketogenesis, fatty acid oxidation, satiety, food intake, thermogenesis, energy expenditure (EE), and bile acid metabolism
In 2009, a novel peptide was characterized by Day et al that combined the antidiabetic and anorexic properties of GLP-1 with the thermogenic and lipolytic effects of glucagon (GCG) in a single molecule based on the GCG backbone [17]
More recent findings have established the value of adding the glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism to that of GLP-1/glucagon receptor (GCGR) [23]. These findings argue for a reevaluation of glucagon as a therapeutic target, a topic highlighted in this Special Issue

Summary

Introduction

Emerging evidence suggests that beyond its counterregulatory role in glucose homeostasis, glucagon regulates a range of actions including lipolysis, ketogenesis, fatty acid oxidation, satiety, food intake, thermogenesis, energy expenditure (EE), and bile acid metabolism. This version was based on the oxyntomodulin sequence and contained full activity at both GLP-1 and GCG receptors and stimulated similar beneficial effects in diet-induced obese (DIO) mice as the “Day” molecule. Following on the heels of these preclinical rodent studies, it was observed that co-administration of GCG and GLP-1 in humans stimulated energy expenditure while reducing GCGR-associated hyperglycemia [19], confirming the translational importance of this strategy.

Results

Conclusion