Sex-specific differences in pancreatic α-cell function

Although sex is a critical biological variable determining physiology, disease risk and therapeutic responses, it remains underrepresented in biomedical research. While sex-dependent differences are well established in cardiovascular and metabolic diseases, their impact on glucagon biology is less understood. Glucagon is the key counter-regulatory hormone to insulin and plays a central role in glucose homeostasis by regulating hepatic glucose production. To date, only a limited number of studies have addressed sex-specific differences in glucagon plasma levels, secretion and α-cell function, indicating that females tend to exhibit a higher glucagon secretion. For the first time, this review summarizes the current literature on glucagon biology suggesting a sex-biased regulation of α-cell activity.