Aryl-hydrocarbon receptor (Ahr) plays an important role in the regulation of intestinal homeostasis.

Diabetes is characterized by vascular complications and intestinal dysfunction. We aimed at understanding the relationship between intestinal defense impairment and inflammation in diabetes and effects of Ahr ligands on diabetes-induced insulin resistance, endovascular inflammation, and intercellular adhesion molecule (ICAM) and flavin mono-oxygenase (FMO3) expression. Effects of Ahr ligands, such as tryptophan (Trp) and indole-3-carbinol (I3C) on intestinal barrier and inflammation of Ins2^Akita mice were examined. Myeloid differentiation primary response 88 (MYD88) is the adaptor for inflammatory signaling pathways. Ins2^Akita-MyD88^-/- mice were used to study the role of MyD88. Ins2^Akita mice demonstrated decreased Ahr and regenerating islet-derived 3-β (Reg3β) expression, and increased Klebsiella pneumoniae translocation. Ins2^Akita mice demonstrated increased inducible nitric oxide synthase (iNOS) expression of intestine; ICAM, iNOS, interleukin 1 beta (IL-1β), and FMO3 expression of liver; and ICAM, iNOS, and FMO3 expression in aorta. Trp and I3C decreased diabetes-induced translocation and increased Ahr and Reg3β expression of intestine. Ahr ligands reduced diabetes-induced ICAM and FMO3 expression in liver and aorta; IL-6, tumor necrosis factor alpha (TNF-α), and iNOS expression in Kupffer cells; plasma IL-6 and TNF-α levels; dipeptidyl peptidase (DPP4) activity; and insulin insensitivity. Ins2^Akita-MyD88^-/- mice demonstrated decreased expression of p-NF-κB of liver and ICAM of aorta compared with Ins2^Akita mice. Altogether, our data suggest that diabetes induces ICAM and FMO3 expression through the decrease in intestinal defense and MyD88. Ahr ligands reverse diabetes-induced intestinal defense impairment, insulin insensitivity, FMO3/ICAM expression, and systemic inflammation.

芳烃受体（Ahr）在肠道动态平衡的调节中起着重要作用。

糖尿病的特征是血管并发症和肠功能障碍。我们旨在了解肠道防御障碍与糖尿病炎症之间的关系，以及Ahr配体对糖尿病诱导的胰岛素抵抗，血管内炎症，细胞间粘附分子（ICAM）和黄素单加氧酶（FMO3）表达的影响。考察了色氨酸（Trp）和吲哚-3-甲醇（I3C）等Ahr配体对Ins2 ^Akita小鼠肠道屏障和炎症的影响。骨髓分化主要反应88（MYD88）是炎症信号通路的适配器。使用Ins2 ^Akita -MyD88 ^-/-小鼠研究MyD88的作用。Ins2^秋田小鼠表现出降低的Ahr和再生的胰岛来源的3-β（Reg3β）表达，并增加了肺炎克雷伯菌的易位性。Ins2 ^Akita小鼠表现出肠道中诱导型一氧化氮合酶（iNOS）表达增加；肝脏的ICAM，iNOS，白介素1β（IL-1β）和FMO3表达；以及ICAM，iNOS和FMO3在主动脉中的表达。Trp和I3C减少糖尿病引起的易位，并增加肠道的Ahr和Reg3β表达。Ahr配体降低了糖尿病诱导的肝脏和主动脉中ICAM和FMO3的表达；IL-6，肿瘤坏死因子α（TNF-α）和iNOS在库普弗细胞中的表达；血浆IL-6和TNF-α水平；二肽基肽酶（DPP4）活性; 和胰岛素不敏感。Ins2^秋田-MyD88 ^-/-与Ins2^秋田小鼠相比，小鼠的肝脏p-NF-κB表达和主动脉ICAM降低。总之，我们的数据表明，糖尿病通过肠防御和MyD88的降低诱导了ICAM和FMO3表达。Ahr配体可逆转糖尿病引起的肠道防御功能受损，胰岛素不敏感性，FMO3 / ICAM表达和全身性炎症。