Diabetes exacerbates inflammatory bowel disease in mice with dietinduced obesity

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 

作者机构：Department of Pediatric Gastroenterology and HepatologySeattle Children’s HospitalSeattleWA 98105United States 不详 Department of Medicinal ChemistryUniversity of WashingtonSeattleWA 98195United States Department of Laboratory Medicine and PathologySeattle Children's HospitalSeattleWA 98105United States 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2023年第29卷第33期

页      面：4991-5004页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：The National Institutes of Health under the National Institute of Diabetes and Digestive and Kidney Diseases(NIHNIDDK),No.DK114474(JMS)and No.DK128383(JMS),No.DK131695(KLF),No.DK101997(MWS),No.DK083042(MWS),No.DK089056(GJM)and No.DK124238(GJM) Department of Defense(JMS),No.W81XWH2110635 The University of Washington Royalty Research Fund(JMS),No.A139339 The NIH-NIDDK T32 Training Grant(KLF),No.DK007742 The NIH-National Heart,Lung,and Blood Institute T32 Training Grant(KMA),No.HL007028 The NIH-NIDDK–funded Diabetes Research Center,No.P30DK017047 The Nutrition Obesity Research Center at the University of Washington,No.P30DK035816 

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

摘      要：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.