Author(s): Korolkiewicz R, Tashima K, Kubomi M, Kato S, Takeuchi K
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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 degrees 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 mm(2)) which could be prevented by insulin or nitric oxide synthase (NOS) inhibitors: aminoguanidine or L-NAME (N(omega)-nitro-L-arginine methyl ester). Mucosal injury was further aggravated by low temperature (51.1 +/- 7.8 mm(2)), 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.
This article was published in Digestion
and referenced in Journal of Diabetes & Metabolism