Loss of angiotensin-converting enzyme 2 leads to impaired glucose homeostasis in mice

被引:87
作者
Niu, Ming-Jia [1 ]
Yang, Jin-Kui [1 ]
Lin, Shan-Shan [1 ]
Ji, Xiu-Juan [1 ]
Guo, Li-Min [1 ]
机构
[1] Capital Med Univ, Dept Endocrinol, Beijing Tongren Hosp, Beijing 100730, Peoples R China
基金
中国国家自然科学基金;
关键词
Angiotensin-converting enzyme 2; Pancreas; Glucose homeostasis; Insulin sensitivity;
D O I
10.1007/s12020-008-9110-x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This study aimed to investigate the role of angiotensin-converting enzyme 2 (ACE2) in regulating glucose homeostasis. Immunohistochemistry was used to investigate ACE2 expression in the pancreas. Glucose tolerance test, insulin secretion test, and insulin tolerance test were performed in age-matched male ACE2 knockout (KO) and wild-type (WT) mice. We found that ACE2 was positively expressed in the pancreas. Male ACE2 KO mice displayed a selective decrease in first-phase insulin secretion in response to glucose and a progressive impairment of glucose tolerance compared with age- and sex-matched WT mice. On the other hand, insulin sensitivity of the peripheral tissue in age-matched ACE2 KO and WT mice showed no difference. These findings suggest that ACE2 might play an important role in glucose homeostasis as well as type 2 diabetes.
引用
收藏
页码:56 / 61
页数:6
相关论文
共 31 条
[11]   Loss of ARNT/HIF1β mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes [J].
Gunton, JE ;
Kulkarni, RN ;
Yim, SH ;
Okada, T ;
Hawthorne, WJ ;
Tseng, YH ;
Roberson, RS ;
Ricordi, C ;
O'Connell, PJ ;
Gonzalez, FJ ;
Kahn, CR .
CELL, 2005, 122 (03) :337-349
[12]   Pancreatic islet blood flow is selectively enhanced by captopril, irbesartan and pravastatin, and suppressed by palmitate [J].
Huang, Zhen ;
Jansson, Leif ;
Sjoholm, Ake .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 346 (01) :26-32
[13]   Role of phosphatidylinositol 3-kinase/Akt pathway in angiotensin II and insulin-like growth factor-1 modulation of nitric oxide synthase in vascular smooth muscle cells [J].
Isenovic, ER ;
Meng, Y ;
Divald, A ;
Milivojevic, N ;
Sowers, JR .
ENDOCRINE, 2002, 19 (03) :287-291
[14]   Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial [J].
Julius, S ;
Kjeldsen, SE ;
Weber, M ;
Brunner, HR ;
Ekman, S ;
Hansson, L ;
Hua, TS ;
Laragh, J ;
McInnes, GT ;
Mitchell, L ;
Plat, F ;
Schork, A ;
Smith, B ;
Zanchetti, A .
LANCET, 2004, 363 (9426) :2022-2031
[15]   Ramipril treatment suppresses islet fibrosis in Otsuka Long-Evans Tokushima fatty rats [J].
Ko, SH ;
Kwon, HS ;
Kim, SR ;
Moon, SD ;
Ahn, YB ;
Song, KH ;
Son, HS ;
Cha, BY ;
Lee, KW ;
Son, HY ;
Kang, SK ;
Park, CG ;
Lee, IK ;
Yoon, KH .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 316 (01) :114-122
[16]   Pdx1 restores β cell function in Irs2 knockout mice [J].
Kushner, JA ;
Ye, J ;
Schubert, M ;
Burks, DJ ;
Dow, MA ;
Flint, CL ;
Dutta, S ;
Wright, CVE ;
Montminy, MR ;
White, MF .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (09) :1193-1201
[17]   Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets [J].
Lau, T ;
Carlsson, PO ;
Leung, PS .
DIABETOLOGIA, 2004, 47 (02) :240-248
[18]   Loss of angiotensin-converting enzyme-2 leads to the late development of angiotensin II-dependent glomerulosclerosis [J].
Oudit, Gavin Y. ;
Herzenberg, Andrew M. ;
Kassiri, Zamaneh ;
Wong, Denise ;
Reich, Heather ;
Khokha, Rama ;
Crackower, Michael A. ;
Backx, Peter H. ;
Penninger, Josef M. ;
Scholey, James W. .
AMERICAN JOURNAL OF PATHOLOGY, 2006, 168 (06) :1808-1820
[19]  
Pagtalunan ME, 2000, J AM SOC NEPHROL, V11, P1278, DOI 10.1681/ASN.V1171278
[20]   Angiotensin II blockade and low-protein diet produce additive therapeutic effects in experimental glomerulonephritis [J].
Peters, H ;
Border, WA ;
Noble, NA .
KIDNEY INTERNATIONAL, 2000, 57 (04) :1493-1501