Incretins are gut hormones that are secreted from enteroendocrine cells into the blood within minutes after eating. One of their many physiological roles is to regulate the amount of insulin that is secreted after eating. In this manner, as well as others to be described in this review, their final common raison d'être is to aid in disposal of the products of digestion. There are two incretins, known as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), that share many common actions in the pancreas but have distinct actions outside of the pancreas. Both incretins are rapidly deactivated by an enzyme called dipeptidyl peptidase 4 (DPP4). A lack of secretion of incretins or an increase in their clearance are not pathogenic factors in diabetes. However, in type 2 diabetes (T2DM), GIP no longer modulates glucose-dependent insulin secretion, even at supraphysiological (pharmacological) plasma levels, and therefore GIP incompetence is detrimental to beta-cell function, especially after eating. GLP-1, on the other hand, is still insulinotropic in T2DM, and this has led to the development of compounds that activate the GLP-1 receptor with a view to improving insulin secretion. Since 2005, two new classes of drugs based on incretin action have been approved for lowering blood glucose levels in T2DM: an incretin mimetic (exenatide, which is a potent long-acting agonist of the GLP-1 receptor) and an incretin enhancer (sitagliptin, which is a DPP4 inhibitor). Exenatide is injected subcutaneously twice daily and its use leads to lower blood glucose and higher insulin levels, especially in the fed state. There is glucose-dependency to its insulin secretory capacity, making it unlikely to cause low blood sugars (hypoglycemia). DPP4 inhibitors are orally active and they increase endogenous blood levels of active incretins, thus leading to prolonged incretin action. The elevated levels of GLP-1 are thought to be the mechanism underlying their blood glucose-lowering effects.

中文翻译：

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肠促胰岛素在葡萄糖稳态和糖尿病治疗中的作用。

肠促胰素是一种肠道激素，在进食后几分钟内从肠内分泌细胞分泌到血液中。它们的众多生理作用之一是调节进食后分泌的胰岛素量。以这种方式，以及本评论中将描述的其他方式，它们的最终共同存在理由是帮助处理消化产物。有两种肠促胰岛素，称为葡萄糖依赖性促胰岛素肽 (GIP) 和胰高血糖素样肽-1 (GLP-1)，它们在胰腺中具有许多共同作用，但在胰腺外具有不同的作用。两种肠降血糖素都被称为二肽基肽酶 4 (DPP4) 的酶迅速失活。肠促胰岛素分泌不足或清除率增加不是糖尿病的致病因素。然而，在 2 型糖尿病 (T2DM) 中，GIP 不再调节葡萄糖依赖性胰岛素分泌，即使在超生理（药理学）血浆水平，因此 GIP 无能对 β 细胞功能有害，尤其是在进食后。另一方面，GLP-1 在 T2DM 中仍然具有促胰岛素作用，这导致开发了激活 GLP-1 受体以改善胰岛素分泌的化合物。自 2005 年以来，基于肠促胰岛素作用的两类新药物已被批准用于降低 T2DM 患者的血糖水平：肠促胰岛素模拟物（艾塞那肽，它是一种有效的 GLP-1 受体长效激动剂）和肠促胰岛素增强剂（西格列汀） ，这是一种 DPP4 抑制剂）。艾塞那肽每天两次皮下注射，其使用会导致血糖降低和胰岛素水平升高，尤其是在进食状态下。其胰岛素分泌能力依赖葡萄糖，因此不太可能导致低血糖（低血糖）。DPP4 抑制剂具有口服活性，它们会增加活性肠降血糖素的内源性血液水平，从而导致肠降血糖素作用延长。GLP-1 水平升高被认为是其降低血糖作用的潜在机制。