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Incretin-based therapies - review of the physiology, pharmacology and emerging clinical experience

机译:基于肠泌素的疗法-生理学,药理学和新兴临床经验的回顾

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摘要

Diabetes therapies based on manipulation of the incretin system are now widely available, with millions of people receiving treatment. The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1 are released from endocrine cells in the small intestinal mucosa primarily in response to oral nutrient ingestion. They have various effects, but those most relevant to metabolic dysfunction include stimulation of insulin and suppression of glucagon secretion, with resultant reduction in fasting and postprandial glucose. Incretin secretion and/or action is impaired in type 2 diabetes, leading to development of strategies aimed at redressing this abnormality. These strategies include pharmacological inhibition of dipeptidyl peptidase-4, the enzyme responsible for the short half-life of endogenous incretins, and administration of long-acting dipeptidyl peptidase-4-resistant peptides that bind to and activate the glucagon-like peptide-1 receptor. In this review, we address aspects of incretin biology and pharmacotherapy with a view to highlighting potentially clinically relevant issues and areas of basic research that may impinge on these.
机译:基于肠降血糖素系统的糖尿病疗法现已广泛可用,数百万人接受治疗。肠促胰岛素,葡萄糖依赖性促胰岛素肽和胰高血糖素样肽-1主要是由于口服营养素摄入而从小肠粘膜的内分泌细胞释放的。它们具有多种作用,但与代谢功能异常最相关的作用包括刺激胰岛素和抑制胰高血糖素分泌,从而导致禁食和餐后葡萄糖减少。在2型糖尿病中肠抑素的分泌和/或作用受损,从而导致开发出旨在纠正这种异常的策略。这些策略包括药理学抑制二肽基肽酶-4(该酶负责内源性肠降血糖素的半衰期短)以及施用长效二肽基肽酶-4-抗性肽,该肽结合并激活胰高血糖素样肽-1受体。在这篇综述中,我们着眼于肠降血糖素生物学和药物治疗的各个方面,以期突出潜在的临床相关问题和可能影响这些问题的基础研究领域。

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