Abstract
We examined the influence of diabetes on the healing of HCl-induced gastric lesions and the healing promoting effect of basic fibroblast growth factor (bFGF) on these lesions under diabetic conditions induced in rats by streptozotocin (70 mg/kg, i.p.). The experiments were performed using 2-wk streptozocin-diabetic rats with blood glucose levels of >300 mg/dl. After 18 hr fasting, these animals were given 1 ml of 0.6 N HCl by gavage, and 1 hr later they were fed normally before being killed on various days after HCl treatment. Recombinant human basic fibroblast growth factor (acid resistant recombinant human basic fibroblast growth factor mutein CS-23: 10 to 1000 ng/kg × 2, p.o.) or insulin (4 U/rat × 1, s.c.) was given 5 days after HCl treatment. Gastric lesions induced by HCl healed to quiescent state within 5 days both macro- and microscopically. Diabetic conditions did not affect the development of HCl-induced gastric lesions but significantly delayed the healing of these lesions. Daily administration of insulin returned high blood glucose levels to within normal ranges (120–140 mg/dl) and significantly antagonized the delayed healing of these lesions. The delayed healing in diabetic rats was also significantly promoted by recombinant human basic fibroblast growth factor (>300 ng/kg × 2) without any effect on blood glucose level. In normal rats, the mucosal levels of bFGF increased significantly in response to gastric injury at 3 days after HCl treatment. The mucosal bFGF levels in streptozotocin-diabetic rats were significantly lower under basal conditions before HCl treatment and did not increase after injury, yet such dysregulation of bFGF production was partially restored by insulin treatment. rhbFGF even at 1000 ng/kg had no effect on gastric acid secretion in either normal or streptozotocin-diabetic rats. These results suggest that diabetic conditions have deleterious influences on the healing of acute gastric lesions in both an insulin- and bFGF-sensitive manner, and that the administration of exogenous bFGF antagonizes the delayed healing of gastric lesions observed in diabetic animals.
Footnotes
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Send reprint requests to: Dr. Koji Takeuchi, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607, Japan.
- Abbreviations:
- bFGF
- basic fibroblast growth factor
- rhbFGF
- recombinant human basic fibroblast growth factor
- STZ
- streptozotocin
- EGF
- epidermal growth factor
- TGF-α
- transforming growth factor-α
- MAb
- monoclonal antibodies
- PBS
- phosphate-buffered saline
- Received June 17, 1996.
- Accepted December 31, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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