State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Periodontology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
J Dent Res. 2020 Jul;99(7):839-846. doi: 10.1177/0022034520911037. Epub 2020 Mar 16.
Insulin resistance is one of the critical pathogeneses of type 2 diabetes mellitus (T2DM). Elevated levels of plasma branched-chain amino acids (BCAAs) are associated with insulin resistance. Recent studies have demonstrated the role of in the development of insulin resistance. However, the mechanisms by which induces insulin resistance are still unclear. The purpose of this study was to investigate whether induces insulin resistance through BCAA biosynthesis. We established a murine model of periodontitis by infecting mice with . Alveolar bone loss, insulin sensitivity, and the plasma level of BCAAs were measured. A BCAA aminotransferase-deficient strain () was constructed, and its kinetic growth, biofilm formation, and in vivo colonization were compared with its wild-type strain. Alveolar bone loss, insulin sensitivity, and the plasma level of BCAAs of the mice infected with either wild-type strain or strain were further measured. We found that periodontal infection with significantly upregulated the plasma level of BCAAs and aggravated the high-fat diet (HFD)-induced insulin resistance. deletion did not alter the growth, biofilm formation, and in vivo colonization of . More important, the strain was unable to upregulate the plasma level of BCAAs and induce insulin resistance in HFD-fed mice. These findings suggest that the BCAA biosynthesis of plays a critical role in the development of insulin resistance in the HFD-fed mice. The BCAA biosynthesis pathways may provide a potential target for the disruption of linkage between periodontitis and T2DM.
胰岛素抵抗是 2 型糖尿病（T2DM）的关键发病机制之一。血浆支链氨基酸（BCAAs）水平升高与胰岛素抵抗有关。最近的研究表明，在胰岛素抵抗的发展中发挥作用。然而，诱导胰岛素抵抗的确切机制尚不清楚。本研究旨在探讨是否通过 BCAA 生物合成诱导胰岛素抵抗。我们通过感染来建立牙周炎的小鼠模型。测量牙槽骨丢失、胰岛素敏感性和血浆 BCAAs 水平。构建了一个 BCAA 转氨酶缺陷株（），并比较了其野生型菌株的动力学生长、生物膜形成和体内定植情况。进一步测量了感染野生型菌株或 菌株的小鼠的牙槽骨丢失、胰岛素敏感性和血浆 BCAAs 水平。我们发现，牙周感染 显著上调血浆 BCAAs 水平，并加重高脂肪饮食（HFD）诱导的胰岛素抵抗。缺失并没有改变的生长、生物膜形成和体内定植。更重要的是，该菌株无法上调血浆 BCAAs 水平，也无法在 HFD 喂养的小鼠中诱导胰岛素抵抗。这些发现表明，BCAA 生物合成在 HFD 喂养的小鼠胰岛素抵抗的发展中起关键作用。BCAA 生物合成途径可能为破坏牙周炎和 T2DM 之间的联系提供一个潜在的靶点。
