Induction of gastric lesions and hypoglycemic response by food deprivation in streptozotocin-diabetic rats

Overnight fasting causes hemorrhagic lesions in the stomach of streptozotocin (STZ)-induced diabetic rats, but the pathogenetic mechanism remains unknown. The present study was performed to investigate the pathogenesis of such lesions developed in STZ-diabetic rats after starvation, mainly in relation to blood glucose changes. A single injection of STZ (70 mg/kg, intraperitoneally) induced hyperglycemic conditions one week after the administration, and high blood glucose levels (BGL: >350 mg%) remained up to three weeks later. The STZ-diabetic rats developed gastric lesions with the marked reduction of BGL after 18 hr of fasting, depending upon the duration of diabetes; the lesion score and BGL reduction in the 3-week-old STZ rats were 32.0±7.8 mm and >250 mg/100 ml, respectively. Acid secretion in the pylorus-ligated rats was not significantly changed in the STZ-induced diabetic conditions for the initial two weeks but slightly decreased at three weeks when compared with normal rats. Fasting of normal rats for 18 hr did not cause either BGL reduction or any lesion in the stomach. In the 3-week-old STZ animals, the severity of gastric lesions increased with the duration of fasting (4–18 hr) and was again closely associated with the degree of BGL reduction. These lesions induced by 18 hr of starvation in 3-week-old STZ rats were significantly inhibited by pretreatment with insulin (4 units/rat/day) for the last one week to maintain BGL within normal ranges or by intravenous infusion of 25% glucose during fasting period. Both of these treatments significantly prevented BGL reduction in response to fasting. These results suggest that gastric lesions induced in STZ-diabetic rats by fasting are insulin-sensitive and may be associated with a profound hypoglycemic response to food deprivation.     

Radioimmunoassay of motilin

A radioimmunoassay method of motilin was developed in our laboratory and was validated in dogs with a platinum monopolar electrode in the duodenum. We confirmed that a bolus infusion of 0.3 M tris-buffer solution or 0.1 N HCl solution in the duodenum produces a significant rise in plasma immunoreactive motilin (IRM) concentrations. This coincided with a marked increase in the percentage of spike potentials on slow waves of the duodenum, similar to phase III of interdigestive myoelectric-activity (MA). A possible relationship between plasma IRM and interdigestive MA of canine duodenum was studied. It was found that cyclic changes occurred in the fasting plasma IRM concentrations in dogs. While the peak motilin concentration was always observed in phase III, the lowest concentration of motilin was found in phase I of interdigestive MA in the duodenum. In dogs with the electrodes in the duodenum and jejunum, the peak IRM concentration did not correlate with phase III of interdigestive MA in the jejunum. A dose of synthetic porcine motilin, 0.06 g/kg/hr, which produced the plasma IRM concentration comparable to the peak fasting motilin concentration, could induce an identical phase III in the duodenum. These observations indicate that there is a relationship between cyclic changes in plasma IRM concentrations and interdigestive MA of the duodenum. It is suggested further that motilin is a hormone which may play an important role in inducing phase III of interdigestive MA in the duodenum.This work was supported by the Gastrointestinal Research Fund at The Genesee Hospital.