Prokinetic effects of a ghrelin receptor agonist GHRP-6 in diabetic mice

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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 tTansit (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.
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