RGD Reference Report - Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats.

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Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats.
Authors:	Chen, Yen-Cheng Ho, Ching-Chun Yi, Chih-Hsun Liu, Xiu-Zhu Cheng, Tzu-Ting Lam, Chen-Fuh
Citation:	Chen YC, etal., PLoS One. 2017 Nov 2;12(11):e0187434. doi: 10.1371/journal.pone.0187434. eCollection 2017.
RGD ID:	13446410
Pubmed:	PMID:29095895 (View Abstract at PubMed)
PMCID:	PMC5667749 (View Article at PubMed Central)
DOI:	DOI:10.1371/journal.pone.0187434 (Journal Full-text)
BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
gastric ulcer	treatment	ISO	Nos3 (Rattus norvegicus)	13446410; 13446410		RGD
gastric ulcer	treatment	IEP		13446410		RGD

Objects Annotated

Genes (Rattus norvegicus)

Nos3 (nitric oxide synthase 3)

Genes (Mus musculus)

Nos3 (nitric oxide synthase 3, endothelial cell)

Genes (Homo sapiens)

NOS3 (nitric oxide synthase 3)

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Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats.