The Emerging Role of CYP17A1 in Diabetes and Related Metabolic Disorders

CYP17A1 (cytochrome P450 17A1) is a key steroidogenic enzyme that catalyzes 17α-hydroxylase and 17,20-lyase reactions, controlling glucocorticoid and androgen production. Emerging evidence suggests that CYP17A1 is not only essential for adrenal and gonadal steroidogenesis, but could also contribute to obesity, insulin resistance, type 2 diabetes, and hypertension. Genetic studies have associated CYP17A1 variants with fasting glucose, type 2 diabetes risk, arterial stiffness, and metabolic syndrome traits. In mouse models, obesity induces hepatic CYP17A1 expression and 17-hydroxyprogesterone overproduction, which activates glucocorticoid receptor signaling, promotes hepatic gluconeogenesis, and exacerbates insulin resistance and hyperglycemia. CYP17A1 has also been linked to adipose tissue dysfunction, altered steroid signaling, and redistribution of fat from visceral to subcutaneous depots. This review summarizes CYP17A1 structure, regulation, protein interaction networks, and its roles in insulin resistance, adipose tissue biology, steroid excess, and vascular complications. It also discusses CYP17A1 genetic variation and the therapeutic potential and limitations of CYP17A1 inhibition and glucocorticoid receptor modulation in diabetes and related metabolic disorders.