Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db Mice
Recent evidence supported the presence of a local renin-angiotensin system (RAS) in the pancreas, which is implicated in many physiological and pathophysiological processes. We utilized small interfering RNA (siRNA) to investigate the effects of angiotensin II type 1 receptor (AT1R) knockdown on glu...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2013/319586 |
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| author | Zhen Zhang Chunyan Liu Zhenhua Gan Xinyi Wang Qiuyan Yi Yanqing Liu Yingzhijie Wang Bin Lu Hong Du Jiaqing Shao Jun Wang |
| author_facet | Zhen Zhang Chunyan Liu Zhenhua Gan Xinyi Wang Qiuyan Yi Yanqing Liu Yingzhijie Wang Bin Lu Hong Du Jiaqing Shao Jun Wang |
| author_sort | Zhen Zhang |
| collection | DOAJ |
| description | Recent evidence supported the presence of a local renin-angiotensin system (RAS) in the pancreas, which is implicated in many physiological and pathophysiological processes. We utilized small interfering RNA (siRNA) to investigate the effects of angiotensin II type 1 receptor (AT1R) knockdown on glucose-stimulated insulin secretion (GSIS) in isolated islets of db/db mice and to explore the potential mechanisms involved. We found that Ad-siAT1R treatment resulted in a significant decrease both in AT1R mRNA level and in AT1R protein expression level. With downexpression of AT1R, notable increased insulin secretion and decreased glucagon secretion levels were found by perifusion. Simultaneously, significant increased protein levels of IRS-1 (by 85%), IRS-2 (by 95%), PI3K(85) (by 112.5%), and p-Akt2 (by 164%) were found by western blot. And upregulation of both GLUT-2 (by 190%) and GCK (by 121%) was achieved after AT1R inhibition by Ad-siAT1R. Intraislet AT1R expression level is a crucial physiological regulator of insulin sensitivity of β cell itself and thus affects glucose-induced insulin and glucagon release. Therefore, the characteristics of AT1R inhibitors could make it a potential novel therapeutics for prevention and treatment of type 2 diabetes. |
| format | Article |
| id | doaj-art-b4e7090ea9d64b539a7f8f4ff68f2d6d |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-b4e7090ea9d64b539a7f8f4ff68f2d6d2025-08-20T03:39:22ZengWileyInternational Journal of Endocrinology1687-83371687-83452013-01-01201310.1155/2013/319586319586Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db MiceZhen Zhang0Chunyan Liu1Zhenhua Gan2Xinyi Wang3Qiuyan Yi4Yanqing Liu5Yingzhijie Wang6Bin Lu7Hong Du8Jiaqing Shao9Jun Wang10Department of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Endocrinology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaDepartment of Cardiology, Jinling Hospital, Southern Medical University, 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, ChinaRecent evidence supported the presence of a local renin-angiotensin system (RAS) in the pancreas, which is implicated in many physiological and pathophysiological processes. We utilized small interfering RNA (siRNA) to investigate the effects of angiotensin II type 1 receptor (AT1R) knockdown on glucose-stimulated insulin secretion (GSIS) in isolated islets of db/db mice and to explore the potential mechanisms involved. We found that Ad-siAT1R treatment resulted in a significant decrease both in AT1R mRNA level and in AT1R protein expression level. With downexpression of AT1R, notable increased insulin secretion and decreased glucagon secretion levels were found by perifusion. Simultaneously, significant increased protein levels of IRS-1 (by 85%), IRS-2 (by 95%), PI3K(85) (by 112.5%), and p-Akt2 (by 164%) were found by western blot. And upregulation of both GLUT-2 (by 190%) and GCK (by 121%) was achieved after AT1R inhibition by Ad-siAT1R. Intraislet AT1R expression level is a crucial physiological regulator of insulin sensitivity of β cell itself and thus affects glucose-induced insulin and glucagon release. Therefore, the characteristics of AT1R inhibitors could make it a potential novel therapeutics for prevention and treatment of type 2 diabetes.http://dx.doi.org/10.1155/2013/319586 |
| spellingShingle | Zhen Zhang Chunyan Liu Zhenhua Gan Xinyi Wang Qiuyan Yi Yanqing Liu Yingzhijie Wang Bin Lu Hong Du Jiaqing Shao Jun Wang Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db Mice International Journal of Endocrinology |
| title | Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db Mice |
| title_full | Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db Mice |
| title_fullStr | Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db Mice |
| title_full_unstemmed | Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db Mice |
| title_short | Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db Mice |
| title_sort | improved glucose stimulated insulin secretion by selective intraislet inhibition of angiotensin ii type 1 receptor expression in isolated islets of db db mice |
| url | http://dx.doi.org/10.1155/2013/319586 |
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