RGD Reference Report - Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity. - Rat Genome Database

RGD Reference Report - Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity. - Rat Genome Database

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Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity.
Authors:	Kooptiwut, Suwattanee Hanchang, Wanthanee Semprasert, Namoiy Junking, Mutita Limjindaporn, Thawornchai Yenchitsomanus, Pa-thai
Citation:	Kooptiwut S, etal., J Endocrinol. 2015 Mar;224(3):215-24. doi: 10.1530/JOE-14-0397. Epub 2014 Dec 15.
RGD ID:	151708735
Pubmed:	PMID:25512346 (View Abstract at PubMed)
DOI:	DOI:10.1530/JOE-14-0397 (Journal Full-text)
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(phox) 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(phox) 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, when cultured in basal glucose, supplementation of testosterone did not have any effect on cell apoptosis, oxidative stress, and expression of AGT1R and p47(phox). 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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Ncf1	Rat	cellular response to glucose stimulus		IEP			RGD
Ncf1	Rat	cellular response to testosterone stimulus		IEP			RGD

Objects Annotated

Genes (Rattus norvegicus)

Ncf1 (neutrophil cytosolic factor 1)

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