Prokinetic effects of a ghrelin receptor agonist GHRP-6 in diabetic mice.
OBJECTIVE
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 microg/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 microg/kg and atropine blocked the prokinetic effects of GHRP-6 on GE and IT.


CONCLUSIONS
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.
Zheng
Qi
Q
Department of General Surgery, The Affiliated Sixth Hospital of Medical School, Shanghai Jiaotong University, Shanghai 200233, China.
Qiu
Wen-Cai
WC
Yan
Jun
J
Wang
Wei-Gang
WG
Yu
Song
S
Wang
Zhi-Gang
ZG
Ai
Kai-Xing
KX
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000503:physiopathology; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009197:Myenteric Plexus / Q000187:drug effects / Q000503:physiopathology; D009842:Oligopeptides / Q000494:pharmacology*; D054440:Receptors, Ghrelin / Q000819:agonists* / Q000378:metabolism
D005765:Gastrointestinal Agents; D018727:Muscarinic Antagonists; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C041048:growth hormone releasing hexapeptide; D001285:Atropine