Glucagon as a Therapeutic Approach to Severe Hypoglycemia: After 100 Years, Is It Still the Antidote of Insulin?

Abstract

Hypoglycemia represents a dark and tormented side of diabetes mellitus therapy. Patients treated with insulin or drug inducing hypoglycemia, consider hypoglycemia as a harmful element, which leads to their resistance and lack of acceptance of the pathology and relative therapies. Severe hypoglycemia, in itself, is a risk for patients and relatives. The possibility to have novel strategies and scientific knowledge concerning hypoglycemia could represent an enormous benefit. Novel available glucagon formulations, even now, allow clinicians to deal with hypoglycemia differently with respect to past years. Novel scientific evidence leads to advances concerning physiopathological mechanisms that regulated glycemic homeostasis. In this review, we will try to show some of the important aspects of this field.

Keywords: diabetes; glucagon; hypoglycemia; therapy.

Figure 1

Potential mechanisms linking hypoglycemia to cardiovascular events.

Figure 2

Hypothetical pathway of glucagon action/modulation on liver. (A) In physiological conditions, blood glucose regulates insulin and glucagon secretion. The equilibrium of these two hormones controls hepatic glucose release. (B) When glucagon is intramuscularly injected, it acts mainly at the hepatic level resulting in the activation of glucose release through glycogen lysis and gluconeogenesis. (C) Nasal glucagon administration could induce actions at the brain levels. In this way, novel potential actions at the hepatic level could regulate hepatic glucose release.