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Diabetes exacerbates inflammatory bowel disease in mice with dietinduced obesity

World Journal of Gastroenterology 2023年第33期29卷 4991-5004页

作者： Kendra L Francis Kimberly m Alonge maria Cristina Pacheco Shannon J Hu Cody A Krutzsch Gregory J morton michael W Schwartz jarrad m scarlett Department of Pediatric Gastroenterology and Hepatology Seattle Children’s HospitalSeattleWA 98105United States 不详 Department of medicinal Chemistry University of WashingtonSeattleWA 98195United States Department of Laboratory medicine and Pathology Seattle Children's HospitalSeattleWA 98105United States

BACKGROUND The increased prevalence of inflammatory bowel disease(IBD)among patients with obesity and type 2 diabetes suggests a causal link between these diseases,potentially involving the effect of hyperglycemia to disrupt intestinal barrier *** To investigate whether the deleterious impact of diabetes on the intestinal barrier is associated with increased IBD severity in a murine model of colitis in mice with and without diet-induced *** mice were fed chow or a high-fat diet and subsequently received streptozotocin to induce diabetic-range *** weeks later,dextran sodium sulfate was given to induce *** select experiments,a subset of diabetic mice was treated with the antidiabetic drug dapagliflozin prior to colitis *** included both clinical and histological measures of colitis activity as well as histochemical markers of colonic epithelial barrier *** In mice given a high-fat diet,but not chow-fed animals,diabetes was associated with significantly increased clinical colitis activity and histopathologic markers of disease *** was also associated with a decrease in key components that regulate colonic epithelial barrier integrity(colonic mucin layer content and epithelial tight junction proteins)in diet-induced obese *** of these effects of diabetes in diet-induced obese mice was ameliorated by restoring *** In obese mice,diabetes worsened clinical and pathologic outcomes of colitis via mechanisms that are reversible with treatment of ***-induced intestinal barrier dysfunction offers a plausible mechanism linking diabetes to increased colitis *** findings suggest that effective diabetes management may decrease the clinical severity of IBD.

关键词： Inflammatory bowel disease Type 2 diabetes Obesity Intestinal barrier Hyperglycemia Colitis in mice Tight junction proteins

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