Increased susceptibility of gastric mucosa to ulcerogenic stimulation in diabetic rats–role of capsaicin‐sensitive sensory neurons

Abstract

1 We examined the gastric mucosal blood¯ow (GMBF) and ulcerogenic responses following barrier disruption induced by sodium taurocholate (TC) in diabetic rats and investigated the role of capsaicinsensitive sensory neurons in these responses. 2 Animals were injected streptozotocin (STZ: 70 mg kg 71 , i.p.) and used after 5, 10 and 15 weeks of diabetes with blood glucose levels of 4350 mg dl 71 . The stomach was mounted on an ex-vivo chamber under urethane anaesthesia and exposed to 20 mM TC plus 50 mM HCl for 30 min in the presence of omeprazole. Gastric transmucosal potential dierence (PD), GMBF, and luminal acid loss (H + backdiusion) were measured before and after exposure to 20 mM TC, and the mucosa was examined for lesions 90 min after TC treatment. 3 Mucosal application of TC caused PD reduction in all groups; the degree of PD reduction was similar between normal and diabetic rats, although basal PD values were lower in diabetic rats. In normal rats, TC treatment caused luminal acid loss, followed by an increase of GMBF, resulting in minimal damage in the mucosa. 4 The increased GMBF responses associated with H + back-diusion were mitigated in STZ-treated rats, depending on the duration of diabetes, and severe haemorrhagic lesions occurred in the stomach after 10 weeks of diabetes. 5 Intragastric application of capsaicin increased GMBF in normal rats, but such responses were mitigated in STZ diabetic rats. The amount of CGRP released in the isolated stomach in response to capsaicin was signi®cantly lower in diabetic rats when compared to controls. 6 The deleterious in¯uences on GMBF and mucosal ulcerogenic responses in STZ-diabetic rats were partially but signi®cantly antagonized by daily insulin (4 units rat 71 ) treatment. 7 These results suggest that the gastric mucosa of diabetic rats is more vulnerable to acid injury following barrier disruption, and this change is insulin-sensitive and may be partly accounted for by the impairment of GMBF response associated with acid back-diusion and mediated by capsaicin-sensitive sensory neurons.

Streptozocin-induced Pancreatic Islet Destruction in Beef Cows

“…However, increased susceptibility of gastric mucosa to ulcergenic stimulation has been noted in STZ-induced diabetic rats. 20 In the present study, gastrointestinal ulceration may have been indirectly associated with STZ secondary to uremia and stress.…”

Possible biochemical effects following inhibition of ethanol-induced gastric mucosa damage byGymnema sylvestrein male Wistar albino rats

“…This may be due to the ability of gymnemic acids to delay the glucose absorption in blood through the small intestine, the exact action being unknown. Several reports indicated that diabetes mellitus increased the mucosal susceptibility to ulcerogenic stimuli and a predisposition to gastric ulceration (Takeuchi et al, 1994;Tashima et al, 1998). In such conditions of co-occurring diabetes and gastric ulcers, it would be better to manage with drugs that have both anti-diabetic and antiulcer activities.…”

Capsaicin and Gastric Ulcers

“…Investigations have been made using invivo stomach, 21 stomach mounted in ex vivo chamber preparations, [22][23][24][25][26][27][28][29][30]32,35,120 stomach chambered with the blood supply intact, 33 glandular stomach of anesthetized rats chambered between two plastic rings, 34 perfused duodenum of anesthetized rats or duodenal loop of rats 23,42 and conscious dogs with duodenal loops and Heidenhain pouches. 44 The administration of capsaicin, various noxious agents, and the assay of certain gastric constituents have been made using rats, dogs, and cats with gastric fistula and gastric cannula, 45−49 anesthetized rats and chronically implanted gastric and duodenal cannula, 50,51,189 awake male beagle dogs with a chronic intra cerebro ventricular (i.c.v) cannula and gastric fistula 52 and anesthetized rats fasted overnight with acutely cannulated cisterna magna.…”

“…264 Gastric blood flow and acid secretion by capsaicin increasing in a parallel manner but not the other way and direct stimulation of the pareital cell causing increase in blood flow were noted. 14 Capsaicin 0.16-6.55 µM/kg administered into the lumen via gastric fistula, 14 i.g., 35,37,54,61,67,130,165,166 topically, 35,75,120,166,265 parenterally, 130 or on perfusion (10-640 µM) of the stomach in anesthetized rats 63 induces hyperemia. The increase in blood flow by capsaicin 1.6 × 10 −4M is the same whether administered i.g.…”