Effects of gastroprokinetic agents on gastroparesis in streptozotocin-induced diabetic rats

Abstract

The influence of diabetic hyperglycemia on solid gastric emptying in rats was examined. Diabetes was produced by streptozotocin (STZ, 40 mg/kg i.v.), and diabetic hyperglycemia was observed from 1 day after the STZ injection. The gastric emptying of glass beads in the diabetic rats was significantly delayed compared with that in age-matched control rats at 1, 3 and 7 days after diabetes induction. A slight decrease in gastric emptying was observed in the diabetic rats from 2 to 52 weeks after the diabetes induction. We also investigated the influence of gastroprokinetic agents on STZ-induced diabetic gastroparesis and subdiaphragmatic vagotomy-induced gastroparesis in rats. The selective 5-HT3 receptor antagonists ramosetron (YM060), YM114 (KAE-393), granisetron and ondansetron, and the substituted benzamides (5-HT4 receptor agonist/5-HT3 receptor antagonists) cisapride mosapride and SC-53116 dose-dependently enhanced gastric emptying in normal rats. These compounds also reversed the impairment of diabetic gastroparesis rats at 7 days after the STZ injection, but higher doses were required. The solid gastric emptying in subdiaphragmatic vagotomized rats was also delayed. Ramosetron and the substituted benzamides cisapride and zacopride partially reversed the gastroparesis in the vagotomized rats. These results suggest that acute hyperglycemia is important mechanism for the delay of solid gastric emptying in diabetic rats. It is also suggested that selective 5-HT3 receptor antagonists and substituted benzamides enhance gastric emptying not only in normal rats but also in diabetic and vagotomized rats.

Improvement of Gastric Motility with Gastric Electrical Stimulation in STZ-Induced Diabetic Rats

“…Delayed gastric emptying was consistently reported within 2 weeks after STZ injection [26], whereas the findings were controversial 4 weeks or more after STZ injection [27, 28]. A recent study by Miyamoto et al [27] reported an accelerated gastric emptying at 4 weeks after STZ injection, whereas in this study, we observed a significant delay in gastric emptying 6 weeks after STZ injection.…”

“…While gastric slow waves have never been studied previously in STZ-diabetic rats, gastric emptying was documented in a number of previous studies [26,27,28] with conflicting results. Delayed gastric emptying was consistently reported within 2 weeks after STZ injection [26], whereas the findings were controversial 4 weeks or more after STZ injection [27, 28].…”

Effects of an Atractylodes lancea rhizome extract and a volatile component β-eudesmol on gastrointestinal motility in mice

“…However, a 5-HT 2C receptor agonist, WAY 161503, had no effect on gastric emptying or gastrointestinal motility. There are reports that 5-HT 3 receptor agonists reduce gastric emptying and gastrointestinal motility (Yamano et al, 1997;Tominaga et al, 2011). Zhang et al (2008) reported that regulative effects of the essential oil of Atractylodes lancea on delayed gastric emptying were performed through the inhibition of the release of central CRF and activation of vagal pathway.…”

Investigation of the influence of pregnancy on the role of nitric oxide in gastric emptying and non-adrenergic non-cholinergic relaxation in the rat

“…Although the gastric emptying of beads is not completely comparable to the emptying of digestible solid food as the beads have to be pushed in toto through the pylorus, the method is used as a measure of solid gastric emptying (Yamano et al 1997). The gastric emptying of the beads did not significantly differ between the 3 investigated groups, although the values ranged from 36 to 69%, illustrating the great variability with this method of testing gastric emptying.…”