caa a22 4500 606236643 CHVBK 20210128101248.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s11010-014-2280-3 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2280-3 Overexpression of angiotensin II type 2 receptor promotes apoptosis and impairs insulin secretion in rat insulinoma cells [Elektronische Daten] [Min Liu, Danqing Jing, Yan Wang, Yu Liu, Shinan Yin] Angiotensin II (Ang II), the major effector hormone of renin-angiotensin system, acts as a promoter of insulin resistance and diabetes mellitus type 2 pathogenesis. Activation of Ang II type 2 receptor (AT2R) has been examined as a potential therapeutic strategy. However, there are conflicting findings regarding the role of AT2R. In the current study, we evaluated the effects of overexpressing AT2R by viral vector transduction on the apoptosis and function of pancreatic β-islet cells. The rat insulinoma cell line, INS-1, was transduced with a recombinant adenoviral vector expressing AT2R (Ad-G-AT2R-EGFP). AT2R overexpression resulted in significantly reduced cell viability and subsequently impaired glucose-stimulated insulin secretion (GSIS) function in INS-1 cells. Down-regulated expressions of GSIS pathway components, insulin, glucose transporter 2, and glucokinase were associated with AT2R overexpression. Further analysis determined that overexpression of AT2R induced G1-phase cell cycle arrest and Ang II-independent apoptotic cell death as indicated by increased Annexin V staining. To understand the apoptosis signaling triggered by AT2R overexpression, levels of caspase proteins were measured. Overexpression of AT2R significantly induced caspase-8, caspase-9, and caspase-3 cleavage, and decreased Bcl-2, pAkt, and pERK expression levels. AT2R-induced cell apoptosis was successfully blocked by the caspase inhibitor Z-VAD-FMK. Our findings suggested that AT2R overexpression triggers the apoptosis of INS-1 cells and dysfunction in insulin secretion. In conclusion, more careful design and consideration are required when applying AT2R-related therapies in treating diabetes. Springer Science+Business Media New York, 2014 Angiotensin II type 2 receptor (AT2R) nationallicence Apoptosis nationallicence Insulin secretion nationallicence Diabetes nationallicence INS-1 cells nationallicence Liu Min Department of Endocrinology, The First Affiliated Hospital of Chinese People's Liberation Army General Hospital, No. 51, Road Fucheng, District Haidian, 100048, Beijing, China aut Jing Danqing Department of Endocrinology, The First Affiliated Hospital of Chinese People's Liberation Army General Hospital, No. 51, Road Fucheng, District Haidian, 100048, Beijing, China aut Wang Yan Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, China aut Liu Yu Department of Geriatric Endocrinology, Chinese People's Liberation Army General Hospital, Beijing, China aut Yin Shinan Department of Endocrinology, The First Affiliated Hospital of Chinese People's Liberation Army General Hospital, No. 51, Road Fucheng, District Haidian, 100048, Beijing, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 233-244 0300-8177 400:1-2<233 2015 400 11010 https://doi.org/10.1007/s11010-014-2280-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2280-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liu Min Department of Endocrinology, The First Affiliated Hospital of Chinese People's Liberation Army General Hospital, No. 51, Road Fucheng, District Haidian, 100048, Beijing, China aut NATIONALLICENCE 700 1- Jing Danqing Department of Endocrinology, The First Affiliated Hospital of Chinese People's Liberation Army General Hospital, No. 51, Road Fucheng, District Haidian, 100048, Beijing, China aut NATIONALLICENCE 700 1- Wang Yan Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, China aut NATIONALLICENCE 700 1- Liu Yu Department of Geriatric Endocrinology, Chinese People's Liberation Army General Hospital, Beijing, China aut NATIONALLICENCE 700 1- Yin Shinan Department of Endocrinology, The First Affiliated Hospital of Chinese People's Liberation Army General Hospital, No. 51, Road Fucheng, District Haidian, 100048, Beijing, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 400/1-2(2015-02-01), 233-244 0300-8177 400:1-2<233 2015 400 11010