Publication: Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity
Issued Date
2015-01-01
Resource Type
ISSN
14796805
00220795
00220795
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2-s2.0-84924777958
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Endocrinology. Vol.224, No.3 (2015), 215-224
Suggested Citation
Suwattanee Kooptiwut, Wanthanee Hanchang, Namoiy Semprasert, Mutita Junking, Thawornchai Limjindaporn, Pa Thai Yenchitsomanus Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity. Journal of Endocrinology. Vol.224, No.3 (2015), 215-224. doi:10.1530/JOE-14-0397 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/35562
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Title
Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity
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Abstract
© 2015 Society for Endocrinology. Hypogonadism in men is associated with an increased incidence of type 2 diabetes. Supplementation with testosterone has been shown to protect pancreatic β-cell against apoptosis due to toxic substances including streptozotocin and high glucose. One of the pathological mechanisms of glucose-induced pancreatic β-cell apoptosis is the induction of the local rennin-angiotensin-aldosterone system (RAAS). The role of testosterone in regulation of the pancreatic RAAS is still unknown. This study aims to investigate the protective action of testosterone against glucotoxicity-induced pancreatic β-cell apoptosis via alteration of the pancreatic RAAS pathway. Rat insulinoma cell line (INS-1) cells or isolated male mouse islets were cultured in basal and high-glucose media in the presence or absence of testosterone, losartan, and angiotensin II (Ang II), then cell apoptosis, cleaved caspase 3 expression, oxidative stress, and expression of angiotensin II type 1 receptor (AGTR1) and p47<sup>phox</sup> mRNA and protein were measured. Testosterone and losartan showed similar effects in reducing pancreatic β-cell apoptosis. Testosterone significantly reduced expression of AGTR1 protein in INS-1 cells cultured in high-glucose medium or high-glucose medium with Ang II. Testosterone decreased the expression of AGTR1 and p47<sup>phox</sup> mRNA and protein in comparison with levels in cells cultured in high-glucose medium alone. Furthermore, testosterone attenuated superoxide production when co-cultured with high-glucose medium. In contrast, whencultured in basal glucose, supplementation of testosterone did not have any effect on cell apoptosis, oxidative stress, and expression of AGT1R and p47<sup>phox</sup>. In addition, high-glucose medium did not increase cleaved caspase 3 in AGTR1 knockdown experiments. Thus, our results indicated that testosterone prevents pancreatic β-cell apoptosis due to glucotoxicity through reduction of the expression of ATGR1 and its signaling pathway.