Review highlights sex-specific differences in pancreatic α-cell function and glucagon secretion

Glucagon, the primary counter-regulatory hormone to insulin, is critical for glucose homeostasis by regulating hepatic glucose production. While sex is a fundamental biological variable influencing disease risk and therapeutic responses, its impact on glucagon biology and α-cell function remains significantly understudied. Despite established sex-dependent differences in cardiovascular and metabolic diseases like MASLD, the specific ways sex influences glucagon plasma levels and secretion have received limited attention, representing a crucial knowledge gap.

This review systematically summarized the current literature on glucagon biology, specifically focusing on studies that addressed sex-specific differences in glucagon plasma levels, secretion, and α-cell function. The authors synthesized findings from a limited number of studies to identify trends and highlight the existing knowledge gaps regarding sex-biased regulation of α-cell activity. The methodology involved a comprehensive search of published research to consolidate evidence on this underrepresented aspect of metabolic physiology.

The review synthesized findings indicating that females generally present with higher glucagon secretion compared to males. This sex-biased regulation of α-cell activity suggests potential differential roles in maintaining glucose homeostasis and responding to metabolic challenges. While specific mechanisms underlying these differences are still being elucidated, the consistent trend across limited studies points to a fundamental biological distinction. The implications extend to how hepatic glucose production is regulated in a sex-dependent manner, potentially influencing susceptibility to conditions like type 2 diabetes or MASLD. The authors emphasize that despite these observations, sex as a biological variable remains significantly underrepresented in glucagon research. > The literature consistently, albeit sparsely, indicates that females tend to exhibit a higher glucagon secretion compared to males.