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World J Gastroenterol. Aug 14, 2008; 14(30): 4795-4799
Published online Aug 14, 2008. doi: 10.3748/wjg.14.4795
Prokinetic effects of a ghrelin receptor agonist GHRP-6 in diabetic mice
Qi Zheng, Wen-Cai Qiu, Jun Yan, Wei-Gang Wang, Song Yu, Zhi-Gang Wang, Kai-Xing Ai
Qi Zheng, Wen-Cai Qiu, Jun Yan, Wei-Gang Wang, Song Yu, Zhi-Gang Wang, Kai-Xing Ai, Department of General Surgery, The Affiliated Sixth Hospital of Medical School, Shanghai Jiaotong University, Shanghai 200233, China
Author contributions: Zheng Q and Qiu WC contributed equally to this work; Zheng Q, Qiu WC and Wang ZG carried out the animal experiment and prepared the paper; Yan J, Wang WG and Yu S participated in the animal experiment; Ai KX helped write, organize, and correct the paper.
Supported by National Natural Science Foundation of China, No. 30400429s
Correspondence to: Zhi-Gang Wang, Department of General Surgery, The Affiliated Sixth Hospital of Medical School, Shanghai Jiaotong University, Shanghai 200233, China. shsmu_cqcq@163.com
Telephone: +86-21-64369181
Received: May 3, 2008
Revised: July 19, 2008
Accepted: July 26, 2008
Published online: August 14, 2008
Abstract

AIM: To investigate the effects of a ghrelin receptor agonist GHRP-6 on delayed gastrointestinal transit in alloxan-induced diabetic mice.

METHODS: A diabetic mouse model was established by intraperitoneal injection with alloxan. Mice were randomized into two main groups: normal mice and diabetic mice treated with GHRP-6 at doses of 0, 20, 50, 100 and 200 μg/kg ip. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) were studied in mice after they had a phenol red meal following injection of GHRP-6. Based on the most effective GHRP-6 dosage, atropine was given at 1 mg/kg for 15 min before the GHRP-6 injection for each measurement. The mice in each group were sacrificed 20 min later and the percentages of GE, IT, and CT were calculated.

RESULTS: Percentages of GE, IT, and CT were significantly decreased in diabetic mice as compared to control mice. In the diabetic mice, GHRP-6 improved both GE and IT, but not CT. The most effective dose of GHRP-6 was 200 μg/kg and atropine blocked the prokinetic effects of GHRP-6 on GE and IT.

CONCLUSION: GHRP-6 accelerates delayed GE and IT, but has no effect on CT in diabetic mice. GHRP-6 may exert its prokinetic effects via the cholinergic pathway in the enteric nervous system, and therefore, has therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.

Keywords: GHRP-6; Diabetes mellitus; Gastric emptying; Intestinal transit; Colonic transit