title: Exogenous insulin-like growth factor (IGF)-1 improves the impaired healing of gastric mucosal lesions in diabetic rats.
abstract: BACKGROUND
  We examined the influence of diabetes mellitus (DM) on the healing of HCl-induced gastric lesions and the healing promoting effect of IGF-1 on these lesions.
  
  
  METHODS
  Experiments were performed on rats injected with streptozotocin (STZ, 70 mg kg(-1), i.p.) 5 weeks prior to the experimental session. Diabetic animals had blood glucose levels (BGLs) higher than 350 mg dl(-1). Randomly chosen rats were treated with insulin (4 IU day(-1) rat(-1)) starting 1 week after STZ. Animals were given 1 ml of 0.6 m HCl by gavage following 18 h of fasting. Normal feeding was started 1 h later. Animals were killed at various time points after HCl. Recombinant human IGF-1 (rhIGF-1) at doses 10-400 microg kg(-1) was injected subcutaneously twice daily for 4 days following HCl treatment.
  
  
  RESULTS
  Gastric lesions induced by HCl healed macroscopically within 10 days. DM and insulin regimen did not affect the development of HCl-invoked gastric lesions. However, DM significantly delayed the healing of such lesions. Daily administration of insulin returned the high BGLs to significantly lower ranges (190-210 mg dl(-1)) and markedly antagonized the delayed healing. Likewise, the repeated administration of rhIGF-1 (>/=10 microg kg(-1)) significantly enhanced the healing of gastric lesions in diabetic rats, without any notable effect on BGLs or gastric acid secretion. The mucosal expression of IGF-1 mRNA was lower in diabetic rat stomachs as compared to normal rats, although the expression was apparently restored after insulin treatment.
  
  
  CONCLUSIONS
  These results suggest that DM has a deleterious influence on the healing of acute gastric lesions in both insulin- and IGF-1-sensitive manner. The systemic administration of rhIGF enhanced the rate of healing of gastric lesions observed in the healing-impaired STZ-diabetic animals.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, 607-8414, Japan.
authors.forename: R P
authors.initials: RP
authors.lastname: Korolkiewicz
authors.forename: K
authors.initials: K
authors.lastname: Tashima
authors.forename: A
authors.initials: A
authors.lastname: Fujita
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000473:pathology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000627:therapeutic use*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I