Regulatory effects of the AMPKα-SIRT1 molecular pathway on insulin resistance in PCOS mice: An in vitro and in vivo study
Autor: | Lisi Cai, Xuanying Deng, Lei Chen, Xin Tao, Shuqi Ge |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
medicine.medical_specialty endocrine system diseases Biophysics Biology AMP-Activated Protein Kinases In Vitro Techniques Biochemistry Cell Line Pathogenesis 03 medical and health sciences Mice 0302 clinical medicine Insulin resistance Sirtuin 1 In vivo Internal medicine medicine Animals Humans Insulin Molecular Biology Mice Inbred BALB C Ovary Cell Biology Molecular pathway medicine.disease female genital diseases and pregnancy complications In vitro 030104 developmental biology Endocrinology Gene Expression Regulation 030220 oncology & carcinogenesis Molecular mechanism Female Insulin Resistance hormones hormone substitutes and hormone antagonists Metabolic Networks and Pathways Compound c Polycystic Ovary Syndrome |
Zdroj: | Biochemical and biophysical research communications. 494(3-4) |
ISSN: | 1090-2104 |
Popis: | In order to preliminarily explore the correlation between the AMPKα-SIRT1 pathway and insulin resistance and reproductive function in PCOS mice and find the pathogenesis molecular mechanism and potential therapeutic target of PCOS, we carried out in vitro study of human granulosa KGN cells and in vivo study of PCOS mouse model which was constructed with DHEA, and AICAR and Compound C were applied. We have found that SIRT1 and AMPKα expression in KGN cells gradually decreased as DHEA concentration increased; Mice of the PCOS model were in an obvious status of IR (P 0.05). Granulosa cells in their ovarian were present in fewer numbers and were disorderly arranged, their numbers of immature follicles were significantly increased, and their AMPKα-SIRT1 pathways were down-regulated. The AMPKα-SIRT1 pathway could be up-regulated after AICAR treatment, resulting in improved IR status (P 0.0001); however, the abovementioned effect was blocked by Compound C. Thus we concluded that the AMPKα-SIRT1 molecular pathway may be a molecular mechanism of IR in PCOS and may serve as a therapeutic target for the development of potential treatments for improving metabolic and reproductive function in PCOS. |
Databáze: | OpenAIRE |
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