Glucagon and the metabolic syndrome

Glucagon is involved in the metabolic syndrome through its effects on the development of Type 2 Diabetes Mellitus (T2DM), hyperglycemia, weight loss, and dyslipidemia. While inappropriate glucagon concentrations in T2DM contribute to hyperglycemia, the catabolic effects of pharmacologic concentrations of glucagon appear to facilitate catabolism and weight loss. Indeed, glucagon antagonist therapy improves blood sugars in T2DM, but has been limited by other metabolic disturbances including hepatic steatosis and weight gain. Harnessing the beneficial effects of glucagon agonism therefore is a desirable goal in obesity. Glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) activation may temper the hyperglycemic effects of glucagon and contribute to increased satiety and weight loss. Understanding the physiologic and pharmacologic actions of glucagon in combination with other proglucagon peptide cleavage products is forefront in the future of diabetes and obesity treatment.