Abstract
BackgroundDiabetes 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 resultsChronic 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.ConclusionAdministration 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.
Highlights
Impaired wound healing in diabetic patients is a considerable burden in clinical care due to susceptible to infection, increased generation of advanced glycation products and delayed formation of granulation tissue
These clinical and experimental investigations underscore that diabetes delays the healing process of peptic ulcers, there are currently no effective clinical therapeutic approaches in addition to the standard antipetic ulcer medicine to accelerate the recovery of peptic ulcer disease (PUD) in diabetic patients
The mean body mass was marginally increased in the control animals, but body mass loss was recorded in diabetic rats with or without receiving Ex4 treatment (Table 1)
Summary
Impaired wound healing in diabetic patients is a considerable burden in clinical care due to susceptible to infection, increased generation of advanced glycation products and delayed formation of granulation tissue. Experimental models demonstrated that peptic ulcer healing was significantly reduced by 300% in diabetic rats with decrease in the gastric mucosal blood flow [6]. These clinical and experimental investigations underscore that diabetes delays the healing process of peptic ulcers, there are currently no effective clinical therapeutic approaches in addition to the standard antipetic ulcer medicine to accelerate the recovery of PUD in diabetic patients. 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
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