Abstract

The aim of this paper is to investigate the effects of ghrelin on delayed gastrointestinal transit in streptozotocin-induced diabetic guinea pigs. A diabetic guinea pig model was produced by intraperitoneal (i. p.) injection of streptozotocin (STZ, 280 mg/kg). Diabetic guinea pigs were randomized into two main groups: normal guinea pigs and ghrelin-treated diabetic guinea pigs with doses of 0, 10, 20, 50 and 100 μg/kg i.p. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) studies were performed in guinea pigs by receiving a phenol red meal following injection of ghrelin. Based on the most effective ghrelin dosage, 1 mg/kg atropine was given 15 min before the ghrelin injection in one group of guinea pigs for each study. The guinea pigs in each group were killed 20 min later, their stomachs, intestines, and colons were harvested immediately, and the amount of phenol red recovered was measured. Percentage of gastric emptying (GE%), intestinal transit (IT%), and colonic transit (CT%) were calculated. We found significantly delayed GE, IT, and CT in the diabetic guinea pigs compared with the control guinea pigs (P < 0.05); ghrelin improved both GE and IT, but not CT in the diabetic guinea pigs; the most effective dose of ghrelin was 100 μg/kg, and atropine blocked the prokinetic effects of ghrelin on GE and IT. These results are potentially significant for the clinical treatment of the delayed gastrointestinal transit in diabetes mellitus. In conclusion, ghrelin accelerates delayed GE and IT, but has no effect on CT in the diabetic guinea pigs. The prokinetic effects of ghrelin are probably exerted via the cholinergic pathway in the enteric nervous system. Ghrelin may have a therapeutic potential for diabetic patients with delayed upper gastrointestinal transit.

Key words: Ghrelin, diabetes mellitus, gastric emptying, gastrointestinal transit.