Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jan 7, 2010; 16(1): 48-55
Published online Jan 7, 2010. doi: 10.3748/wjg.v16.i1.48
Atrial natriuretic peptide signal pathway upregulated in stomach of streptozotocin-induced diabetic mice
Zhang-Xun Qiu, Bing Mei, Yi-Song Wu, Xu Huang, Zuo-Yu Wang, Yan-Fei Han, Hong-Li Lu, Young-Chul Kim, Wen-Xie Xu
Zhang-Xun Qiu, Yi-Song Wu, Xu Huang, Zuo-Yu Wang, Yan-Fei Han, Hong-Li Lu, Wen-Xie Xu, Department of Physiology, Shanghai Jiao Tong University, School of Medicine, Shanghai 200240, China
Bing Mei, Shanghai Institute of Brain Functional Genomics; Department of Environmental Science and Technology, East China Normal University, Shanghai 200240, China
Young-Chul Kim, Department of Physiology, Chungbuk National University College of Medicine, 12 Gaeshin-dong, Hungduk-gu, Cheongju, Chungbuk 361-763, South Korea
Author contributions: Qiu ZX, Mei B, Wu YS, Huang X, Wang ZY, Han YF, Lu HL, Kim YC performed the majority of experiments and data analysis; Xu WX designed the study and wrote the manuscript.
Supported by National Natural Science Foundation of China, No. 10672103 and 30360031
Correspondence to: Wen-Xie Xu, MD, PhD, Department of Physiology, Shanghai Jiaotong University School of Medicine, 800 Dongchuan Road, 328 Wenxuan Medical Building, Shanghai 200240, China. wenxiexu@sjtu.edu.cn
Telephone: +86-21-34205639 Fax: +86-21-34201118
Received: October 4, 2009
Revised: November 6, 2009
Accepted: November 13, 2009
Published online: January 7, 2010

AIM: To investigate atrial natriuretic peptide (ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A) pathway and diabetic gastroparesis.

METHODS: Male imprinting control region (ICR) mice (4 wk old) were divided into two groups: control mice, and streptozotocin-induced diabetic mice. Eight weeks after injection, spontaneous gastric contraction was recorded by using physiography in control and streptozotocin-induced diabetic mice. The ANP-positive cells in gastric mucosa and among dispersed gastric epithelial cells were detected by using immunohistochemistry and flow cytometry, respectively. ANP and natriuretic peptide receptor type A (NPR-A) gene expression in gastric tissue was observed by using the reverse transcriptase polymerase chain reaction.

RESULTS: The frequency of spontaneous gastric contraction was reduced from 12.9 ± 0.8 cycles/min in the control group to 8.4 ± 0.6 cycles/min in the diabetic mice (n = 8, P < 0.05). However, the amplitude of contraction was not significantly affected in the diabetic group. The depletion of interstitial cells of Cajal in the gastric muscle layer was observed in the diabetic mice. ANP-positive cells were distributed in the gastric mucosal layer and the density index of ANP-positive cells was increased from 20.9 ± 2.2 cells/field in control mice to 51.8 ± 2.9 cells/field in diabetic mice (n = 8, P < 0.05). The percentage of ANP-positive cells among the dispersed gastric epithelial cells was increased from 10.0% ± 0.9% in the control mice to 41.2% ± 1.0% in the diabetic mice (n = 3, P < 0.05). ANP and NPR-A genes were both expressed in mouse stomach, and the expression was significantly increased in the diabetic mice.

CONCLUSION: These results suggest that the ANP/NPR-A signaling pathway is upregulated in streptozotocin-induced diabetic mice, and contributes to the development of diabetic gastroparesis.

Keywords: Diabetes mellitus, Atrial natriuretic peptide, Gastric mucosa, Gastroparesis