Polaprezine exerts a salutary effect on impaired healing of acute gastric lesions in diabetic rats

We examined the influence of diabetes mellitus (DM) on the healing of HCl-i nduced gastric lesions and the healing promoting effect of polaprezinc [N-( 3-aminopropionyl)-6-histiclinnto zinc] on these lesions. Studies were perfo rmed on rats injected intraperitoneally with streptozotocin (STZ, 70 mg/kg) five weeks prior to experiments. Diabetic rats had blood glucose levels (B GLs) higher than 350 mg/100 ml. Randomly chosen animals were treated subcut aneously with insulin (4 IU/day/rat) starting 1 week after STZ. Animals wer e given 1 ml of 0.6 N HCl by oral gavage (per os) following 18 hr of fastin g; they were fed normally from 1 hr later and killed at various lime points after HCl administration. Polaprezinc (3-30 mg/kg) or its components ZnSO4 /7H(2)O and L-carnosine were given orally, twice daily fur four days follow ing HCl treatment. Gastric lesions induced by HCl healed macroscopically to quiescence within 10 days. DM and insulin did not affect the development o f HCl-invoked gastric lesions, but the healing of such lesions was markedly impaired in animals with DM. Daily administration of insulin returned high BGLs to significantly lower ranges (190-208 mg/100 ml) and markedly antago nized the healing impairment. Polaprezinc (> 10 mg/kg) significantly revers ed the delay observed in diabetic rats without any notable effects on BGLs or acid secretion, Similar trends were observed with 1 ZnSO4/7H(2)O or a mi xture of ZnSQ4/7H(2)O and L-carnosine, but not by L-carnosine alone. The mu cosal expression of insulin-like growth factor-1 (IGF-I) mRNA was significa ntly lower in diabetic rats, a dysregulation partially corrected by insulin and polaprezinc. In addition, the delayed healing in diabetic rats was als o significantly promoted by the repeated subcutaneous administration of rhI GF-I (> 10 mu g/kg, twice daily) without any notable effect on BGLs or acid secretion. These results suggest that DM exerted a deleterious influence o n the healing of acute gastric lesions in both insulin- and zinc-sensitive manner. The salutary effects of polaprezinc on the impaired healing of gast ric lesion in STZ-diabetic animals may at least be partly explained by enha ncement of mucosal IGF-I mRNA expression in the stomach.