Increased Susceptibility of Diabetic Rat Gastric Mucosa to Food Deprivation during Cold Stress

Abstract

Background: We investigated the mechanisms responsible for the increased susceptibility of diabetic rat gastric mucosa to damage inflicted by overnight food deprivation (18 h) and its worsening by the cold restraint stress (4°C, 3 h). Methods: Gastric damage was measured in fasted animals, some of which were rendered diabetic by a single intraperitoneal injection of streptozotocin (STZ; 70 mg/kg) 5 weeks before experiments (STZ 5W). Results: STZ 5W rodents showed a number of hemorrhagic lesions in corpus mucosa (26.8 ± 5.2 mm²) which could be prevented by insulin or nitric oxide synthase (NOS) inhibitors: aminoguanidine or L-NAME (N^ω-nitro-L-arginine methyl ester). Mucosal injury was further aggravated by low temperature (51.1 ± 7.8 mm²), the damage ameliorated by insulin, aminoguanidine, or L-NAME. The salutary actions of L-NAME were L-arginine sensitive. Low temperature and L-NAME did not significantly influence the gastric secretory parameters in normal rats. On the other hand, L-NAME and aminoguanidine counteracted the attenuation of gastric juice acidity and acid output in STZ 5W rodents. Blood plasma nitrite and nitrate levels and outputs in gastric juice were augmented in STZ 5W animals in comparison to controls. The total activities of NOS including inducible NOS but not constitutive NOS were markedly enhanced by fasting and cold restraint in gastric mucosa of STZ 5W animals (2.2- and 3.7- or 2.4- and 17.9-fold respectively). Conclusions: Stressful stimuli, such as food bereavement and cold challenge contribute to the elevated susceptibility of diabetic gastric mucosa to damage, even though the main aggressive factor, i.e., gastric acid secretion, is attenuated. The enhanced production of nitric oxide by inducible NOS during food deprivation and cold exposure seems to play an important role in gastric mucosal integrity disturbances during diabetes.

PYY-Tag Transgenic Mice Displaying Abnormal (H+-K+)ATPase Activity and Gastric Mucosal Barrier Impairment

“…As observed in our study, an increased susceptibility of gastric mucosa to damage caused by stressful stimuli (fasting) with concurrent reduction of the gastric acid and mucus secretion has been reported in streptozotocin-diabetic rats (Igarashi et al, 2000;Korolkiewicz et al, 1999). Interestingly, high PYY levels have been found in several gastrointestinal disorders including diabetes gastroenteropathy (El-Salhy et al, 2002).…”

Capsaicin and Gastric Ulcers

“…Food deprivation causes enhanced production of NO by the constitutive nitric oxide synthase (cNOS) which has an important role in disturbing gastric mucosal integrity. 405 In rats with (SZN) -induced diabetes, SP content increases in the thoracic, abdominal aortas and proximal mesenteric artery affecting the vascular system, which is corrected by treatment with insulin. 434…”

Effects of leptin on stress-induced changes of caspases in rat gastric mucosa

“…Group 2 (stress group) animals, after 7 days of PBS injections (i.p. ), were exposed on the eighth day to cold-restraint stress, infl icted by placing the rat in a wire cage at 4.0 ± 0.5°C for 4 h. 28,29 Group 3 (leptin group) received 10 µg/kg recombinant rat leptin (Calbiochem, La Jolla, CA, USA) dissolved in PBS (i.p.) daily for 7 days.…”