Intracrine Testosterone Activation in Human Pancreatic Beta-Cells Stimulates Insulin Secretion

The study found that human pancreatic β-cells express enzymes that convert testosterone (T) to dihydrotestosterone (DHT) and estradiol (E2), which are necessary for the enhancement of glucose-stimulated insulin secretion (GSIS). The conversion of T to DHT and E2 was shown to be inhibited by 5α-reductase and aromatase inhibitors, respectively. The research suggests that these inhibitors could affect GSIS and potentially predispose older men to type 2 diabetes, while in women with androgen excess, intracrine androgen activation may contribute to β-cell dysfunction. The study concludes that β-cells in human pancreatic islets can locally activate sex steroids from circulating testosterone, which is crucial for their role in insulin secretion.