REVIEW article
Front. Endocrinol.
Sec. Diabetes: Molecular Mechanisms
The Role of PYY in Improving Insulin Resistance
Provisionally accepted
- 1First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
- 2Heilongjiang University of Chinese Medicine, Harbin, China
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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 signalling 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.
Keywords: Glucose homeostasis, Insulin Resistance, intestinal hormones, PYY, Y2Receptor
Received: 10 Jan 2026; Accepted: 30 Jan 2026.
Copyright: © 2026 Liu, Ren, Zhang and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jian Ma
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