INDUCTION OF GASTRIC-LESIONS AND HYPOGLYCEMIC RESPONSE BY FOOD-DEPRIVATION IN STREPTOZOTOCIN-DIABETIC RATS

Overnight fasting causes hemorrhagic lesions in the stomach of strepto zotocin (STZ) -induced diabetic rats, but the pathogenetic mechanism r emains unknown. The present study was performed to investigate the pat hogenesis of such lesions developed in STZ-diabetic rats after starvat ion, mainly in relation to blood glucose changes. A single injection o f STZ (70 mg/kg, intraperitoneally) induced hyperglycemic conditions o ne week after the administration, and high blood glucose levels (BGL: >350 mg%) remained up to three weeks later. The STZ-diabetic rats deve loped gastric lesions with the marked reduction of BGL after 18 hr of fasting, depending upon the duration of diabetes; the lesion score and DELTABGL reduction in the 3-week-old STZ rats were 32.0 +/- 7.8 mm an d >250 mg/100 ml, respectively. Acid secretion in the pylorus-ligated rats was not significantly changed in the STZ-induced diabetic conditi ons for the initial two weeks but slightly decreased at three weeks wh en 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-wee k-old STZ animals, the severity of gastric lesions increased with the duration of fasting (4-18 hr) and was again closely associated with th e degree of DELTABGL reduction. These lesions induced by 18 hr of star vation in 3-week-old STZ rats were significantly inhibited by pretreat ment with insulin (4 units/rat/day) for the last one week to maintain BGL within normal ranges or by intravenous infusion of 25% glucose dur ing fasting period. Both of these treatments significantly prevented B GL reduction in response to fasting. These results suggest that gastri c lesions induced in STZ-diabetic rats by fasting are insulin-sensitiv e and may be associated with a profound hypoglycemic response to food deprivation.