Androgen receptor: a new player associated with apoptosis and proliferation of pancreatic beta-cell in type 1 diabetes mellitus.

Author(s): Li, Ru-Jiang; Qiu, Shu-Dong; Wang, Hai-Xu; Tian, Hong; Wang, Li-Rong; Huo, Yong-Wei

Source: Apoptosis Volume: 13 Issue: 8 Pages: 959-71 Published: 2008 Aug

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Abstract: Androgen receptor (AR) mediates a wide range of cellular processes, such as proliferation, differentiation and apoptosis. Here we sought to identify whether AR was located in pancreatic beta-cells and investigate its functions in type 1 diabetes induced by multiple low doses of streptozotocin. Double/triple immunofluorescence, Western blot and semi-quantitative RT-PCR were carried out to determine variances of AR expression in beta-cells and correlation between AR and apoptosis/proliferation of beta-cells with progress of diabetes. In addition, in vitro primary beta-cells from control mice were cultured for 3 days or 6 days with compound stimulation in order to further identify effect of AR on beta-cell apoptosis and proliferation. AR expression in beta-cells peaked in control and 1-day diabetic mice, gradually and significantly decreased, even disappeared in diabetic mice with progress of diabetes. TUNEL-positive beta-cells were concomitant with overexpression of AR, and Ki67-positive beta-cells showed extremely weak, even negative AR staining. In vitro, AR could mediate beta-cell apoptosis, and AR antagonist flutamide contributed to beta-cell proliferation. In conclusion, AR is abundantly expressed in pancreatic beta-cell cytoplasm of control mice. With progress of type 1 diabetes, decrement of AR expression in diabetic mice contributes to prohibit beta-cells from apoptosis, and is strongly associated with beta-cell proliferation.

PubMed ID: 18543106

Document Type: Journal Article; Research Support, Non-U.S. Gov't

Language: English

Address: Department of Anatomy and Histo-Embryology, Key Laboratory of Environment and Genes Related to Disease (Ministry of Education), Medical School of Xi'an Jiaotong University, No. 76 Yanta West Road, Xi'an, 710061, China.

Citation Subset: Index Medicus

ISSN: 1573-675X

NLM Unique ID: 9712129

Country: United States

Date Created: 14 Jul 2008