Volume 18, Issue 3 (8-2026)                   IJDO 2026, 18(3): 239-246 | Back to browse issues page

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Nosrati Andevari A. The Role of Irisin in Type 2 Diabetes: Mechanisms and Therapeutic Implications. IJDO 2026; 18 (3) :239-246
URL: http://ijdo.ssu.ac.ir/article-1-1065-en.html
Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Abstract:   (30 Views)
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by decreased insulin sensitivity, impaired glucose homeostasis, and progressive pancreatic β-cell dysfunction. In addition to insulin and glucagon-like peptide-1 (GLP-1), the secretion of other hormones has emerged as a vital regulator of metabolic health, with potential implications for the prevention and treatment of T2DM. One of the hormones in question is irisin. It is a myokine substantially secreted by skeletal muscle during exercise. The aim of this study is to determine the roles of irisin in T2DM, along with its associated mechanisms and therapeutic implications. Irisin levels are declined in T2DM. Irisin enhances insulin secretion and sensitivity in T2DM, which is associated with improved glycemic indices. Medications such as sitagliptin, metformin, and simvastatin stimulate the release of irisin.
 
Keywords: T2DM, Irisin, Insulin, Glycemic
     
Type of Study: Research | Subject: Special
Received: 2026/08/22 | Accepted: 2026/08/19 | Published: 2026/08/19

References
1. Andevari AN, Moein S, Qujeq D, Moazezi Z, Tilaki KH. The effect of atorvastatin on the concentrations of methylglyoxal, glyoxalase 1, and aldo-keto reductase family 1 member B10 in patients with type 2 diabetes mellitus and prediabetes. International Journal of Diabetes in Developing Countries. 2024;44(2):400-8. [DOI:10.1007/s13410-023-01249-6]
2. Andevari AN, Moein S, Qujeq D, Moazezi Z, Hajian-Tilaki K. The effects of atorvastatin consumption on biochemical variables in patients with type 2 diabetes mellitus and pre-diabetes. International Journal of Medical Laboratory. 2022;9(3):198-208.
3. Andevari AN, Firoozjaee AH, Meftah N, Asciabari HA, Bahri F, Shahandashti NE. The effects of atorvastatin consumption on blood levels of sortilin, glycemic, and lipid indices in type 2 diabetic patients: A randomized clinical trial. International Journal of Diabetes in Developing Countries. 2025:1-8. [DOI:10.1007/s13410-025-01557-z]
4. Hou Q, Song R, Zhao X, Yang C, Feng Y. Lower circulating irisin levels in type 2 diabetes mellitus patients with chronic complications: A meta-analysis. Heliyon. 2023;9(11):e21859. [DOI:10.1016/j.heliyon.2023.e21859]
5. Wang R, Liu H. Association between serum irisin and diabetic nephropathy in patients with type 2 diabetes mellitus: a meta-analysis. Hormone and Metabolic Research. 2021;53(05):293-300. [DOI:10.1055/a-1475-4444]
6. Zhang X, Hu C, Wu HM, Ma ZG, Tang QZ. Fibronectin type III domain-containing 5 in cardiovascular and metabolic diseases: a promising biomarker and therapeutic target. Acta Pharmacologica Sinica. 2021;42(9):1390-400. [DOI:10.1038/s41401-020-00557-5]
7. Maak S, Norheim F, Drevon CA, Erickson HP. Progress and challenges in the biology of FNDC5 and irisin. Endocrine reviews. 2021;42(4):436-56. [DOI:10.1210/endrev/bnab003]
8. Martinez Munoz IY, Camarillo Romero ED, Garduno Garcia JD. Irisin a novel metabolic biomarker: present knowledge and future directions. International journal of endocrinology. 2018;2018(1):7816806. [DOI:10.1155/2018/7816806]
9. Shaban SM, Gamal RM, Hasan NM, Mohammed HS. Investigating Atherosclerosis by Using Serum Irisin in Patients with Ankylosing spondylitis. Sohag Medical Journal. 2025;29(1):125-38. [DOI:10.21608/smj.2025.351135.1525]
10. Jedrychowski MP, Wrann CD, Paulo JA, Gerber KK, Szpyt J, Robinson MM,et al. Detection and quantitation of circulating human irisin by tandem mass spectrometry. Cell metabolism. 2015;22(4):734-40. [DOI:10.1016/j.cmet.2015.08.001]
11. Polyzos SA, Mathew H, Mantzoros CS. Irisin: a true, circulating hormone. Metabolism-Clinical and Experimental. 2015;64(12):1611-8. [DOI:10.1016/j.metabol.2015.09.001]
12. Marrano N, Biondi G, Borrelli A, Cignarelli A, Perrini S, Laviola L, et al. Irisin and incretin hormones: Similarities, differences, and implications in type 2 diabetes and obesity. Biomolecules. 2021;11(2):286. [DOI:10.3390/biom11020286]
13. Chen JQ, Fang LJ, Song KX, Wang XC, Huang YY, Chai SY, et al. Serum irisin level is higher and related with insulin in acanthosis nigricans-related obesity. Experimental and Clinical Endocrinology & Diabetes. 2016;124(03):203-7. [DOI:10.1055/s-0035-1565060]
14. Zheng S, Chen N, Kang X, Hu Y, Shi S. Irisin alleviates FFA induced β-cell insulin resistance and inflammatory response through activating PI3K/AKT/FOXO1 signaling pathway. Endocrine. 2022;75(3):740-51. [DOI:10.1007/s12020-021-02875-y]
15. Liu S, Du F, Li X, Wang M, Duan R, Zhang J, et al. Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells. PloS one. 2017 Apr 10;12(4):e0175498. [DOI:10.1371/journal.pone.0175498]
16. Gora IM, Ciechanowska A, Ladyzynski P. NLRP3 inflammasome at the interface of inflammation, endothelial dysfunction, and type 2 diabetes. Cells. 2021;10(2):314. [DOI:10.3390/cells10020314]
17. Palideh A, Vaghari-Tabari M, Andevari AN, Qujeq D, Asemi Z, Alemi F, et al. MicroRNAs and periodontal disease: helpful therapeutic targets?. Advanced Pharmaceutical Bulletin. 2022;13(3):423. [DOI:10.34172/apb.2023.048]
18. Zhou J, Yan S, Guo X, Gao Y, Chen S, Li X, et al. Salidroside protects pancreatic β-cells against pyroptosis by regulating the NLRP3/GSDMD pathway in diabetic conditions. International Immunopharmacology. 202;114:109543. [DOI:10.1016/j.intimp.2022.109543]
19. Li T, Yang J, Tan A, Chen H. Irisin suppresses pancreatic β cell pyroptosis in T2DM by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis. Diabetology & Metabolic Syndrome. 2023;15(1):239. [DOI:10.1186/s13098-023-01216-5]
20. Andevari AN, Moein S, Qujeq D, Moazezi Z, Tilaki KH. Effects of atrovastatin on concentrations of 3-hydroxy-3-methylglutaryl-coenzyme A-reductase (HMG-CoA-R), proprotein convertase subtilisin/kexin type 9 (PCSK9) and sortilin in patients with type 2 diabetes mellitus and pre-diabetics. Journal of Nephropathology. 2020 Jul 2;10(1):e05. [DOI:10.34172/jnp.2021.05]
21. Chen SP, Lin SR, Chen TH, Ng HS, Yim HS, Leong MK, et al. Mangosteen xanthone γ-mangostin exerts lowering blood glucose effect with potentiating insulin sensitivity through the mediation of AMPK/PPARγ. Biomedicine & Pharmacotherapy. 2021;144:112333. [DOI:10.1016/j.biopha.2021.112333]
22. Lee HJ, Lee JO, Kim N, Kim JK, Kim HI, Lee YW, et al. Irisin, a novel myokine, regulates glucose uptake in skeletal muscle cells via AMPK. Molecular endocrinology. 2015;29(6):873-81. [DOI:10.1210/me.2014-1353]
23. Zhi S, Yang L, Yang G, Qin C, Yan X, Niu M, et al. Irisin regulates hepatic glucose metabolism via AMPK and PI3K/Akt activation. Aquaculture Nutrition. 2022;2022(1):1946960. [DOI:10.1155/2022/1946960]
24. Li R, Li Y, Yang X, Hu Y, Yu H, Li Y. Reducing VEGFB accelerates NAFLD and insulin resistance in mice via inhibiting AMPK signaling pathway. Journal of Translational Medicine. 2022;20(1):341. [DOI:10.1186/s12967-022-03540-2]
25. Chae SA, Du M, Zhu MJ, Son JS. Exercise enhances placental labyrinth trophoblast development by activation of PGC-1α and FNDC5/irisin. Biology of Reproduction. 2024;110(2):355-64. [DOI:10.1093/biolre/ioad151]
26. Qian L, Zhu Y, Deng C, Liang Z, Chen J, Chen Y, et al. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases. Signal transduction and targeted therapy. 2024;9(1):50. [DOI:10.1038/s41392-024-01756-w]
27. Guo Y, Zhou F, Fan J, Wu T, Jia S, Li J, et al. Swimming alleviates myocardial fibrosis of type II diabetic rats through activating miR-34a-mediated SIRT1/PGC-1α/FNDC5 signal pathway. PLoS One. 2024;19(9):e0310136. [DOI:10.1371/journal.pone.0310136]
28. Hu N, Chen X, Chen C, Liu X, Yi P, Xu T, et al. Exploring the role of esketamine in alleviating depressive symptoms in mice via the PGC-1α/irisin/ERK1/2 signaling pathway. Scientific Reports. 2023;13(1):16611. [DOI:10.1038/s41598-023-43684-9]
29. Shen S, Liao Q, Chen X, Peng C, Lin L. The role of irisin in metabolic flexibility: beyond adipose tissue browning. Drug Discovery Today. 2022;27(8):2261-7. [DOI:10.1016/j.drudis.2022.03.019]
30. Shi H, Hao X, Sun Y, Zhao Y, Wang Y, Cao X, et al. Exercise‐inducible circulating extracellular vesicle irisin promotes browning and the thermogenic program in white adipose tissue. Acta Physiologica. 2024;240(3):e14103. [DOI:10.1111/apha.14103]
31. Luo X, Li J, Zhang H, Wang Y, Shi H, Ge Y, et al. Irisin promotes the browning of white adipocytes tissue by AMPKα1 signaling pathway. Research in veterinary science. 2022;152:270-6. [DOI:10.1016/j.rvsc.2022.08.025]
32. Rodríguez C, Muñoz M, Contreras C, Prieto D. AMPK, metabolism, and vascular function. The FEBS Journal. 2021;288(12):3746-71. [DOI:10.1111/febs.15863]
33. Chen Y, Liao T, Zhou XC, Zeng N, Wang HN, Yan ZP, et al. Irisin protects against IL-1β-induced chondrocytes injury by activating the ERK signaling pathway. 2022. [DOI:10.21203/rs.3.rs-1730641/v1]
34. Wang Y, Tian M, Tan J, Pei X, Lu C, Xin Y, et al. Irisin ameliorates neuroinflammation and neuronal apoptosis through integrin αVβ5/AMPK signaling pathway after intracerebral hemorrhage in mice. Journal of Neuroinflammation. 2022;19(1):82. [DOI:10.1186/s12974-022-02438-6]
35. Ding J, Nguyen AT, Lohman K, Hensley MT, Parker D, Hou L, et al. LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes. The Journal of clinical investigation. 2024 ;134(10):e173278. [DOI:10.1172/JCI173278]
36. Tang H, Yu R, Liu S, Huwatibieke B, Li Z, Zhang W. Irisin inhibits hepatic cholesterol synthesis via AMPK-SREBP2 signaling. EBioMedicine. 2016;6:139-48. [DOI:10.1016/j.ebiom.2016.02.041]
37. Liang N, Li YM, He Z, Hao W, Zhao Y, Liu J, et al. Rutin and quercetin decrease cholesterol in HepG2 cells but not plasma cholesterol in hamsters by oral administration. Molecules. 2021;26(12):3766. [DOI:10.3390/molecules26123766]
38. Tarboush NA, Abu-Yaghi NE, Al Ejeilat LH, Wahed RK, Jeris IN. Association of irisin circulating level with diabetic retinopathy: a case-control study. Experimental and Clinical Endocrinology & Diabetes. 2021 Jan;129(01):36-42. [DOI:10.1055/a-0723-3749]
39. Xuan X, Lin J, Zhang Y, Zhou L, Xu L, Jia J, et al. Serum irisin levels and clinical implication in elderly patients with type 2 diabetes mellitus. Journal of Clinical Medicine Research. 2020;12(9):612. [DOI:10.14740/jocmr4261]
40. Wang Q, Ma L, Zhang Y, Zhang L, An Y, Liu J, et al. Effect of sitagliptin on serum irisin levels in patients with newly diagnosed type 2 diabetes mellitus. Diabetes Therapy. 2021;12(4):1029-39. [DOI:10.1007/s13300-021-01023-z]
41. Li DJ, Huang F, Lu WJ, Jiang GJ, Deng YP, Shen FM. Metformin promotes irisin release from murine skeletal muscle independently of AMP‐activated protein kinase activation. Acta physiologica. 2015;213(3):711-21. [DOI:10.1111/apha.12421]
42. Teaney NA, Cyr NE. FoxO1 as a tissue-specific therapeutic target for type 2 diabetes. Frontiers in endocrinology. 2023;14:1286838. [DOI:10.3389/fendo.2023.1286838]
43. Liu TY, Shi CX, Gao R, Sun HJ, Xiong XQ, Ding L, et al. Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes. Clinical science. 2015;129(10):839-50. [DOI:10.1042/CS20150009]
44. Jamialahmadi T, Baratzadeh F, Reiner Ž, Simental-Mendía LE, Xu S, Susekov AV, et al. The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low‐Density Lipoprotein Levels: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials. Mediators of inflammation. 2021;2021(1):9661752. [DOI:10.1155/2021/9661752]
45. Gouni-Berthold I, Berthold HK, Huh JY, Berman R, Spenrath N, Krone W, et al. Effects of lipid-lowering drugs on irisin in human subjects in vivo and in human skeletal muscle cells ex vivo. PloS one. 2013;8(9):e72858. [DOI:10.1371/journal.pone.0072858]

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