Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1991321 | The Journal of Steroid Biochemistry and Molecular Biology | 2015 | 13 Pages |
Abstract
Although insulin resistance is recognized to contribute to the reproductive and metabolic phenotypes of polycystic ovary syndrome (PCOS), pancreatic beta cell dysfunction plays an essential role in the progression from PCOS to the development of type 2 diabetes. However, the role of insulin secretory abnormalities in PCOS has received little attention. In addition, the precise changes in beta cells and the underlying mechanisms remain unclear. In this study, we therefore attempted to elucidate potential mechanisms involved in beta cell alterations in a rat model of PCOS. Glucose-induced insulin secretion was measured in islets isolated from DHT-treated and control rats. Oxygen consumption rate (OCR), ATP production, and mitochondrial copy number were assayed to evaluate mitochondrial function. Glucose-stimulated insulin secretion is significantly decreased in islets from DHT-treated rats. On the other hand, significant reductions are observed in the expression levels of several key genes involved in mitochondrial biogenesis and in mitochondrial OCR and ATP production in DHT-treated rat islets. Meanwhile, we found that androgens can directly impair beta cell function by inducing mitochondrial dysfunction in vitro in an androgen receptor dependent manner. For the first time, our study demonstrates that increased androgens in female rats can impair glucose-stimulated insulin secretion partly through disruption of pancreatic beta cell mitochondrial function. This work has significance for hyperandrogenic women with PCOS: excess activation of the androgen receptor by androgens may provoke beta cell dysfunction via mitochondrial dysfunction.
Keywords
DHTperoxisome proliferator-activated receptor γ coactivator 1αNADH dehydrogenase subunit 1ND3GSISND1NRF1TFAMPGC-1αINS5α-DihydrotestosteroneMitochondrial DNASmall interfering RNAsiRNAinsulinGlucose-stimulated insulin secretiontestosteroneMinminutemtDNAHourPancreatic beta cellPolycystic ovary syndromeNuclear respiratory factor 1mitochondrial transcription factor AMitochondrial functionNADH dehydrogenase subunit 3Androgen Receptor
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Authors
Hongdong Wang, Xiaping Wang, Yunxia Zhu, Fang Chen, Yujie Sun, Xiao Han,