Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non-alcoholic fatty liver disease.
Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non-alcoholic fatty liver disease.
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DOI：
10.1111/apt.12084
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发表时间：
2012-11
影响因子：
7.6
通讯作者：
Loomba R
中科院分区：
文献类型：
--
作者：
Zarrinpar A;Loomba R
最近的研究引起了人们对肠道和肝脏在2型糖尿病（T2 DM）中的作用的兴趣。综述胃肠道系统在葡萄糖稳态中的作用，特别关注肠促胰岛素激素、肝脂肪变性和胆汁酸的作用。使用肠促胰岛素、葡萄糖依赖性促胰岛素多肽（GIP）、胰高血糖素样肽-1（GLP-1）、二肽基肽酶-4（DPP-4）、肝脂肪变性、胆汁酸和胃旁路等术语检索PubMed和Google Scholar。通过审查文章的参考文献列表，识别出其他相关参考文献。肠促胰岛素激素和胆汁酸分泌的扰动有助于T2 DM的发病机制，从而使其成为潜在的治疗靶点。肠促胰岛素激素（GIP和GLP-1）被DPP-4灭活。GLP-1激动剂和DPP-4抑制剂可改善T2 DM患者的血糖控制。肝脏脂肪变性，沿着胰岛素抵抗，可能先于2型糖尿病的发展，并可能从抗糖尿病药物中获益。胆汁酸在葡萄糖稳态中起重要作用，其作用通过法尼醇X受体（FXR）和细胞表面G蛋白偶联受体TGR 5介导。胆汁酸螯合剂考来维仑已被证明可有效改善T2 DM患者的血糖控制。胃旁路手术后胃肠道解剖结构的改变也可能影响胆汁酸的肝肠再循环，并有助于改善血糖控制。结论：近年来的研究已经导致了在葡萄糖稳态中发挥作用的新途径和过程，以及T2 DM的新治疗靶点和选择。
Recent research has led to an interest in the role of the gut and liver in type 2 diabetes mellitus (T2DM). To review the role of the gastrointestinal system in glucose homeostasis, with particular focus on the effects of incretin hormones, hepatic steatosis, and bile acids. PubMed and Google Scholar were searched using terms such as incretin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), dipeptidyl peptidase-4 (DPP-4), hepatic steatosis, bile acid, and gastric bypass. Additional relevant references were identified by reviewing the reference lists of articles. Perturbations of incretin hormones and bile acid secretion contribute to the pathogenesis of T2DM, leading to their potential as therapeutic targets. The incretin hormones (GIP and GLP-1) are deactivated by DPP-4. GLP-1 agonists and DPP-4 inhibitors improve glycemic control in patients with T2DM. Hepatic steatosis, along with insulin resistance, may precede the development of T2DM, and may benefit from antidiabetes medications. Bile acids play an important role in glucose homeostasis, with effects mediated via the farnesoid X receptor (FXR) and the cell surface G protein-coupled receptor TGR5. The bile acid sequestrant colesevelam has been shown to be effective in improving glycemic control in patients with T2DM. Altered gastrointestinal anatomy after gastric bypass surgery may also affect enterohepatic recirculation of bile acids and contribute to improved glycemic control. Conclusions: Research in recent years has led to new pathways and processes with a role in glucose homeostasis, and new therapeutic targets and options for T2DM.
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