The gastrointestinal tract — the largest endocrine network in human physiology — orchestrates signals from the external environment to maintain neural and hormonal control of homeostasis. Advances in understanding entero-endocrine cell biology in health and disease have important translational relevance. The gut-derived incretin hormone glucagon-like peptide 1 (GLP-1) is secreted upon meal ingestion and controls glucose metabolism by modulating pancreatic islet cell function, food intake and gastrointestinal motility, amongst other effects. The observation that the insulinotropic actions of GLP-1 are reduced in type 2 diabetes mellitus (T2DM) led to the development of incretin-based therapies — GLP-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors — for the treatment of hyperglycaemia in these patients. Considerable interest exists in identifying effects of these drugs beyond glucose-lowering, possibly resulting in improved macrovascular and microvascular outcomes, including in diabetic kidney disease. As GLP-1 has been implicated as a mediator in the putative gut–renal axis (a rapid-acting feed-forward loop that regulates postprandial fluid and electrolyte homeostasis), direct actions on the kidney have been proposed. Here, we review the role of GLP-1 and the actions of associated therapies on glucose metabolism, the gut–renal axis, classical renal risk factors, and renal end points in randomized controlled trials of GLP-1 receptor agonists and DPP-4 inhibitors in patients with T2DM.

中文翻译：

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GLP-1和肾脏：从生理学，药理学到糖尿病的结局

胃肠道-人类生理学中最大的内分泌网络-协调来自外部环境的信号，以维持神经和激素对稳态的控制。了解肠内分泌细胞生物学在健康和疾病方面的进展具有重要的翻译意义。进餐时会分泌肠源性肠降血糖素激素胰高血糖素样肽1（GLP-1），并通过调节胰岛细胞功能，食物摄入和胃肠动力等来控制葡萄糖代谢。在2型糖尿病（T2DM）中GLP-1的促胰岛素作用降低的观察结果导致开发了基于肠降血糖素的疗法-GLP-1受体激动剂和二肽基肽酶4（DPP-4）抑制剂-用于治疗这些患者的血糖过高。在确定这些药物除降低血糖以外的作用方面存在相当大的兴趣，这可能导致改善的大血管和微血管结局，包括在糖尿病性肾脏疾病中。由于GLP-1被认为是假定的肠-肾轴（调节饮食后液体和电解质稳态的快速作用前馈环）的介体，因此已经提出了对肾脏的直接作用。在这里，我们回顾了GLP-1受体激动剂和DPP-4抑制剂的随机对照试验中GLP-1的作用以及相关疗法对葡萄糖代谢，肠-肾轴，经典肾病危险因素和肾终点的作用。在患有T2DM的患者中。包括糖尿病肾病。由于GLP-1被认为是假定的肠-肾轴（调节饮食后液体和电解质稳态的快速作用前馈环）的介体，因此已经提出了对肾脏的直接作用。在这里，我们回顾了GLP-1受体激动剂和DPP-4抑制剂的随机对照试验中GLP-1的作用以及相关疗法对葡萄糖代谢，肠-肾轴，经典肾病危险因素和肾终点的作用。在患有T2DM的患者中。包括糖尿病肾病。由于GLP-1被认为是假定的肠-肾轴（调节饮食后液体和电解质稳态的快速作用前馈环）的介体，因此已经提出了对肾脏的直接作用。在这里，我们回顾了GLP-1受体激动剂和DPP-4抑制剂的随机对照试验中GLP-1的作用以及相关疗法对葡萄糖代谢，肠-肾轴，经典肾病危险因素和肾终点的作用。在患有T2DM的患者中。