Characterization of a Novel Aldose Reductase Inhibitor, TAT, and Its Effects on Streptozotocin-Induced Diabetic Neuropathy in Rats

Inukai, Shinji; Agata, Mitsuji; Sato, Manami; Naitou, Akira; Matsukawa, Hiroaki; Goto, Masayoshi

doi:10.1254/jjp.61.221

Cited by 14 publications

(1 citation statement)

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“…In diabetic patients, peripheral or autonomic neuropathy is thought to be an important factor in the pathogenesis of gastroparesis (Hongo and Okuno 1993;Farrell and Keeffe 1995;Undeland et al 1996). However, it was reported that it took two weeks to induce motor nerve dysfunction after STZ injection in rats (Inukai et al 1992;Mizuno et al 1992). Therefore, mechanisms other than neuropathy are suggested to be involved in the early diabetic gastroparesis in STZ-treated rats.…”

Section: Discussionmentioning

confidence: 99%

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

Yamano¹,

Kamato²,

Nagakura³

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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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.

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