Gut peptides and type 2 diabetes mellitus treatment.
Gut peptides and type 2 diabetes mellitus treatment.
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DOI：
10.1007/s11892-003-0079-9
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发表时间：
2003-10-01
影响因子：
4.2
通讯作者：
Ahren, Bo
中科院分区：
文献类型：
--
作者：
Ahren, Bo
肠道在内分泌细胞中表达肽激素，在自主神经中表达神经肽。这些肽中的几种具有刺激胰岛素分泌的能力。肠促胰岛素是指在进食后释放并在餐后刺激胰岛素分泌的肠道激素。在人类中，葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽-1（GLP-1）是最重要的肠促胰岛素。已经考虑了这些促胰岛素肠肽用于治疗糖尿病的潜在用途。这对于GLP-1是最成功的，GLP-1通过刺激胰岛素分泌、增加β细胞质量、抑制胰高血糖素分泌、延迟胃排空和诱导饱腹感在2型糖尿病受试者中发挥抗糖尿病性质。然而，GLP-1被酶二肽基肽酶IV（DPPIV）快速降解，由于半衰期非常短，使其作为治疗剂没有吸引力。克服这一困难的成功策略是使用DPPIV耐药GLP-1受体激动剂，如NN 2211或exendin-4，以及使用DPPIV抑制剂，如NVPDPP 728和P32/98。这两种方法在临床研究中进行了探索。
The gut expresses peptide hormones in endocrine cells and neuropeptides in autonomic nerves. Several of these peptides have the ability to stimulate insulin secretion. Gut hormones that are released after meal ingestion and stimulate insulin secretion postprandially are called incretins. In humans, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the most important incretins. The potential use of these insulinotropic gut peptides for the treatment of diabetes has been considered. This has been most successful for GLP-1, which exerts antidiabetogenic properties in subjects with type 2 diabetes by stimulating insulin secretion, increasing beta-cell mass, inhibiting glucagon secretion, delaying gastric emptying, and inducing satiety. However, GLP-1 is rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV), making it unattractive as a therapeutic agent because of a very short half-life. Successful strategies to overcome this difficulty are the use of DPPIV-resistant GLP-1 receptor agonists, such as NN2211 or exendin-4, and the use of inhibitors of DPPIV, such as NVPDPP728 and P32/98. These two approaches are explored in clinical investigations.