Insulin Metabolism in Polycystic Ovary Syndrome: Secretion, Signaling, and Clearance

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Its heterogeneous clinical presentation is characterized by hyperandrogenemia, reproductive changes, polycystic ovary morphology, and insulin resistance (IR). The primary pathophysiological process in its multifactorial etiology has not yet been identified. However, the two most proposed core etiologies are the disruption of insulin metabolism and hyperandrogenemia, both of which begin to intertwine and propagate each other in the later stages of the disease. Insulin metabolism can be viewed as the interconnectedness of beta cell function, IR or insulin sensitivity, and insulin clearance. Previous studies of insulin metabolism in PCOS patients have yielded conflicting results, and literature reviews have focused mainly on the molecular mechanisms and clinical implications of IR. In this narrative review, we comprehensively explored the role of insulin secretion, clearance, and decreased sensitivity in target cells as a potential primary insult in PCOS pathogenesis, along with the molecular mechanism behind IR in PCOS.

Keywords: PCOS; beta cell function; glucose homeostasis; insulin clearance; insulin resistance; insulin signaling pathway; polycystic ovary syndrome.

Figure 1

Disrupted insulin metabolism resulting in hyperinsulinemia as an essential pathophysiological driver in PCOS development.

Figure 2

Insulin signaling pathway in PCOS. Unknown intracellular serine kinases may phosphorylate serine residues of insulin receptor and IRS, impairing the phosphorylation of tyrosine residues and signal transduction after stimulation with insulin. This renders the metabolic PI3K pathway defective, while the mitogenic MAPK pathway functions normally.