Diabetes exacerbates inflammatory bowel disease in mice with dietinduced obesity

查看全文 作　　者：Kendra L [1]Francis;Kimberly M [2,3]Alonge;Maria Cristina [4]Pacheco;Shannon J [2]Hu;Cody A [2]Krutzsch;Gregory J [2]Morton;Michael W [2]Schwartz;Jarrad M [1]Scarlett

机构地区：[1]Department of Pediatric Gastroenterology and Hepatology,Seattle Children’s Hospital,Seattle,WA 98105,United States;[2]不详;[3]Department of Medicinal Chemistry,University of Washington,Seattle,WA 98195,United States;[4]Department of Laboratory Medicine and Pathology,Seattle Children's Hospital,Seattle,WA 98105,United States

出　　处：《World Journal of Gastroenterology》索引2023年第29卷第33期,共14页

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. 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 integrity.AIM 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 obesity.METHODS Mice were fed chow or a high-fat diet and subsequently received streptozotocin to induce diabetic-range hyperglycemia.Six weeks later,dextran sodium sulfate was given to induce colitis.In select experiments,a subset of diabetic mice was treated with the antidiabetic drug dapagliflozin prior to colitis onset.Endpoints included both clinical and histological measures of colitis activity as well as histochemical markers of colonic epithelial barrier integrity.RESULTS 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 severity.Diabetes 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 mice.Each of these effects of diabetes in diet-induced obese mice was ameliorated by restoring normoglycemia.CONCLUSION In obese mice,diabetes worsened clinical and pathologic outcomes of colitis via mechanisms that are reversible with treatment of hyperglycemia.Hyperglycemia-induced intestinal barrier dysfunction offers a plausible mechanism linking diabetes to increased colitis severity.These 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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Diabetes exacerbates inflammatory bowel disease in mice with dietinduced obesity

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