Insulin-induced gastric ulcers in the rat.
Low doses of insulin (less than 1.25 IU/kg body weight) stimulate gastric acid secretion in the rat, whereas higher doses (greater than 2.5 IU/kg) release gastrin and cause gastric ulcers but do not increase acid secretion. In this study we have characterized the ulcerogenic properties of insulin in the rat. A dose of 5 IU/kg subcutaneously proved to be maximally effective. Ulcer formation was rapid, and the maximum 90% incidence was reached after 5 h. Both glucose administration and food intake protected against the ulcerogenic effects of insulin. The effects of anti-ulcer drugs and of vagotomy on insulin-induced ulcers were also studied. Animals were divided into seven groups: 1) saline, 2) omeprazole, 3) ranitidine, 4) sucralfate, 5) bilateral vagotomy, 6) unilateral vagotomy, and 7) antrectomy. Medical treatment was continued for 6 days before insulin administration, operations having been performed 6-8 weeks earlier. Insulin was injected subcutaneously in a dose of 5 IU/kg. Five hours later stomachs were inspected for ulcers. Neither the antrectomized rats nor those treated with omeprazole or ranitidine had ulcers. In the saline- and the sucralfate-treated groups the gastric ulcer incidence was 83% and 80%, respectively, with a mean of six and seven ulcers per rat. Ulcers were evenly distributed between the two sides of the stomach. Rats that had undergone bilateral vagotomy (which abolishes gastric acid secretion and causes hypergastrinemia) responded to insulin with an ulcer incidence of 5%. In the unilaterally vagotomized rats there were only 2 ulcers on the denervated compared with 37 on the innervated side.(ABSTRACT TRUNCATED AT 250 WORDS)
Axelson
J
J
Dept. of Surgery, University of Lund, Sweden.
Håkanson
R
R
Hedenbro
J L
JL
D000818:Animals; D005753:Gastric Mucosa / Q000473:pathology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D011706:Pyloric Antrum / Q000601:surgery; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D013392:Sucralfate / Q000494:pharmacology; D014628:Vagotomy
D007328:Insulin; D012965:Sodium Chloride; D013392:Sucralfate; D011899:Ranitidine; D009853:Omeprazole