Insulin-Induced Gastric Ulcers in the Rat

Abstract

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)

The effects of long-lasting hypoglycemia on male reproductive organs in rats

“…Nevertheless, abnormal clinical signs and body weight changes were not observed in the animals exhibiting testicular changes. With respect to the localized reddish discoloration observed on the stomach, gastric ulcers are known to be caused by insulin administration to fasted rats (Axelson et al, 1987). It should be noted that the testicular changes were observed irrespective of the observed stomach changes.…”

The Role of Methylglyoxal-Modified Proteins in Gastric Ulcer Healing

“…In these investigations, the mechanism underlying the increased susceptibility of the gastric mucosa in diabetic animals to damage was multifactorial, and involved increased inflammatory cytokines, decreased gastric blood flow at the ulcer margin, decreased biosynthesis of endogenous prostaglandins in the gastric mucosa, impaired function of heat shock protein (HSP) in the gastric mucosa, and suppression of growth factor production in the gastric mucosa. Furthermore, it has been well known that hyperinsulinemia is associated with type 2 diabetes, it has been demonstrated that over-dose insulin induced gastric ulcer in rats [9,10]. Increased insulin in diabetic animals may be involved with gastric ulcer healing.…”