Emerging role of testosterone in pancreatic β cell function and insulin secretion

One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose homeostasis by testosterone in male and females. Severe testosterone deficiency predisposes men to type 2 diabetes (T2D), while in contrast, androgen excess predisposes women to hyperglycemia. The role of androgen deficiency and excess in promoting visceral obesity and insulin resistance in men and women respectively is well established. However, although it is established that hyperglycemia requires beta cell dysfunction to develop, the role of testosterone in beta cell function is less understood. This review discusses recent evidence that the androgen receptor (AR) is present in male and female beta cells. In males, testosterone action on AR in beta cells enhances glucose-stimulated insulin secretion by potentiating the insulinotropic action of glucagonlike peptide-1. In females, excess testosterone action via AR in beta cells promotes insulin hypersecretion leading to oxidative injury, which in turn predisposes to T2D.