The role of PYY in improving insulin resistance

Insulin resistance (IR) is closely related to type 2 diabetes (T2DM) and metabolic syndrome, which poses a serious challenge globally. In terms of IR treatment, peptide YY holds broad therapeutic potential. The study found that the lack of peptide YY (PYY) is closely related to the occurrence of IR. Therefore, PYY plays an important role in glucose homeostasis and improving insulin sensitivity. Specifically, the two primary circulating forms, PYY(1-36) and PYY(3-36), mediate distinct effects through different neuropeptide Y receptors (YRs). PYY(3-36) predominantly acts through the Y2 receptor (Y2R) in the hypothalamus to suppress appetite and in peripheral tissues (adipose, skeletal muscle, liver) to enhance insulin sensitivity. In contrast, PYY(1-36) acts as a broader agonist, with significant effects on pancreatic β-cell protection and insulin secretion fine-tuning via the Y1 receptor. In addition, PYY(3-36) promotes weight loss by suppressing appetite and delaying gastric emptying, thus improving insulin resistance. This review aims to clarify the biological characteristics and signaling mechanism of PYY, and explore its potential applications in improving insulin resistance. Finally, it will explore the new treatment possibilities of PYY for IR and metabolic diseases based on current research progress.