glucagon-like-peptide-1 and Stomach-Ulcer

Diabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats.. Chronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 μg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area.. Administration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes.

Topics: Animals; Chronic Disease; Diabetes Mellitus, Experimental; Exenatide; Glucagon-Like Peptide 1; Hypoglycemic Agents; Peptides; Rats; Stomach Ulcer; Streptozocin; Venoms; Wound Healing

Intracerebroventricular glucagon-like peptide- 1 (GLP-1) has been shown to prevent the gastric mucosal lesions induced by reserpine. In the present study, we aimed to investigate the contribution of 1- the cholinergic pathway, 2- the sympathetic pathway, 3- somatostatin and 4- endogenous nitric oxide to this gastroprotective effect.. Rats were equipped with intravenous and intracerebroventricular cannulas under ether anesthesia for drug delivery. Rats were pretreated with mecamylamine (5 mg/kg; i.p.) and atropine sulfate (1 mg/kg; i.p.), yohimbine (1 mg/kg; i.p.), cysteamine (280 mg/kg; s.c.), and NG-nitro-L-arginine methyl ester (3 mg/kg; i.v.) to investigate the role of the cholinergic pathway, sympathetic pathway, somatostatin and endogenous nitric oxide, respectively, in the gastroprotective effect of GLP-1. To produce gastric mucosal lesions, reserpine was administered intraperitoneally at a dose of 25 mg/kg in 10 ml/kg of 0.5% acetic acid solution. Four hours later, the animals were decapitated, and their stomachs were removed and scored for mucosal damage.. Glucagon- like peptide-1 (100 ng/10 microl; i.c.v.) inhibited the reserpine-induced gastric mucosal damage by 90% (p<0.01). Neither the nicotinic receptor antagonist mecamylamine (5 mg/kg; i.p.) nor the muscarinic receptor antagonist atropine sulfate (1 mg/kg; i.p) affected the gastroprotective activity of GLP-1. On the other hand, pretreatment with yohimbine, an alpha2-adrenergic receptor antagonist (1 mg/kg; i.p.), cysteamine, a somatostatin depletor (280 mg/kg; s.c.), and NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor (3 mg/kg; i.v.), significantly abolished the protective effect of GLP-1 on reserpine-induced gastric mucosal lesions (p<0.001, p<0.01 and p<0.01, respectively).. We conclude that the sympathetic pathway, somatostatin and nitric oxide, but not the cholinergic pathway, contribute to the gastroprotective effect of intra-cerebroventricular GLP-1 on reserpine-induced gastric mucosal lesions.

Topics: Adrenergic Uptake Inhibitors; Animals; Female; Glucagon-Like Peptide 1; Nitric Oxide; Rats; Rats, Sprague-Dawley; Reserpine; Somatostatin; Stomach Ulcer; Sympathetic Nervous System

Glucagon-like peptide-1 (GLP-1) is accepted to be a peptide involved in the central regulation of gastrointestinal function, but its potential gastroprotective effect is not clear. The aim of this study was to investigate whether intracerebroventricularly injected GLP-1 has protective effects on gastric mucosal lesions induced by several models, and if yes, whether these effects are due to the gastric antisecretory effect of the peptide. GLP-1 which was injected in three different doses (1, 10, 100 ng/10 microl; i.c.v.) to conscious rats prevented the mucosal lesions induced by reserpine and ethanol, but did not prevent the gastric mucosal lesions induced by pyloric ligation. In addition, 1 ng/10 microl dose of centrally injected GLP-1 inhibited gastric acid secretion in pylorus-ligated rats. As a result, we conclude that intracerebroventricularly injected GLP-1 may play a role in the prevention of gastric mucosal lesions induced by certain experimental models and this gastroprotective effect may be independent from its antisecretory effect.

Topics: Animals; Disease Models, Animal; Female; Gastric Acidity Determination; Gastric Mucosa; Glucagon; Glucagon-Like Peptide 1; Hydrogen-Ion Concentration; Injections; Peptide Fragments; Protein Precursors; Rats; Rats, Sprague-Dawley; Stomach Ulcer