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Decreased Insulin Resistance by Myo-Inositol Is Associated with Suppressed Interleukin 6/Phospho-STAT3 Signaling in a Rat Polycystic Ovary Syndrome Model

Journal of Medicinal Food 2020년 23권 4호 p.375 ~ 387
Zhang Yulong, Li Changzhong, Zhang Wenhui, Zheng Xiangqin, Chen Xiujuan,
소속 상세정보
 ( Zhang Yulong ) - Shandong University Shandong Provincial Hospital Department of Obstetrics and Gynecology
 ( Li Changzhong ) - Shandong University Shandong Provincial Hospital Department of Obstetrics and Gynecology
 ( Zhang Wenhui ) - Fujian Medical University Fujian Provincial Maternity and Children’s Hospital Department of Obstetrics and Gynecology
 ( Zheng Xiangqin ) - Fujian Medical University Fujian Provincial Maternity and Children’s Hospital Department of Obstetrics and Gynecology
 ( Chen Xiujuan ) - Fujian Medical University Fujian Provincial Maternity and Children’s Hospital Department of Obstetrics and Gynecology

Abstract


Myo-inositol supplementation may reduce insulin resistance (IR) with few serious side effects in patients with polycystic ovary syndrome (PCOS). To explore the mechanism of this action in an animal model, a PCOS-IR rat model was generated. Enzyme-linked immunosorbent assay was used to assess changes in ovulation function during treatment with a myo-inositol supplement, and Western blotting, real-time polymerase chain reaction, and immunohistochemistry were performed to investigate the underlying molecular mechanisms. The results showed that the myo-inositol supplement decreased the homeostatic model assessment of insulin resistance (HOMA-IR) index and significantly decreased the serum levels of luteinizing hormone (LH), LH/follicle-stimulating hormone ratio, and testosterone, while increasing the serum level of estradiol. Upregulation of interleukin 6 (IL-6), phospho-STAT3 (p-STAT3), Mir-21, and Mir-155 and significant downregulation of PPAR-γ and GLUT4 were detected in the untreated PCOS-IR rat model. However, downregulation of IL-6, p-STAT3, miR-21, and miR-155 and significant upregulation of PPAR-γ and GLUT4 were detected with myo-inositol supplementation. Thus, myo-inositol supplementation may reduce Mir-21 and Mir-155 levels by downregulating IL-6 and p-STAT3 and, subsequently, reverse the expression of PPAR-γ and GLUT4, leading to a decreased HOMA-IR index. In conclusion, the identification of an IL-6/p-STAT3/Mir-155/Mir-21/PPAR-γ/GLUT4 system in the PCOS-IR rat model provides insight into the pathogenesis of PCOS and may indicate a possible therapeutic strategy. Amelioration of the basal serum glucose levels and of the HOMA/HOMA-IR index may be achieved by the reversal of the expression of PPAR-γ and GLUT4 through the downregulation of IL-6, p-STAT3, miR-21, and miR-155 with myo-inositol supplementation.

키워드

insulin resistance; myo-inositol supplement; polycystic ovary syndrome; rat model

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