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胰淀素激动剂:治疗糖尿病的新方法。

Amylin agonists: a novel approach in the treatment of diabetes.

作者信息

Schmitz Ole, Brock Birgitte, Rungby Jorgen

机构信息

Department of Clinical Pharmacology, The Bartholin Building, University of Aarhus, DK 8000 Aarhus C, Denmark.

出版信息

Diabetes. 2004 Dec;53 Suppl 3:S233-8. doi: 10.2337/diabetes.53.suppl_3.s233.

Abstract

Amylin is a peptide hormone that is cosecreted with insulin from the pancreatic beta-cell and is thus deficient in diabetic people. It inhibits glucagon secretion, delays gastric emptying, and acts as a satiety agent. Amylin replacement could therefore possibly improve glycemic control in some people with diabetes. However, human amylin exhibits physicochemical properties predisposing the peptide hormone to aggregate and form amyloid fibers, which may play a part in beta-cell destruction in type 2 diabetes. This obviously makes it unsuitable for pharmacological use. A stable analog, pramlintide, which has actions and pharmacokinetic and pharmacodynamic properties similar to the native peptide, has been developed. The efficacy and safety of pramlintide administration has been tested in a vast number of clinical trials. Approximately 5,000 insulin-treated patients have received pramlintide and approximately 250 for > or =2 years. The aims of this review are to 1) briefly describe actions of amylin as demonstrated in animal and human models and 2) primarily review results from clinical trials with the amylin analog pramlintide.

摘要

胰淀素是一种与胰岛素从胰腺β细胞共同分泌的肽类激素,因此糖尿病患者体内缺乏该激素。它能抑制胰高血糖素分泌,延缓胃排空,并起到饱腹感因子的作用。因此,补充胰淀素可能会改善一些糖尿病患者的血糖控制。然而,人胰淀素具有一些物理化学性质,易使该肽类激素聚集并形成淀粉样纤维,这可能在2型糖尿病的β细胞破坏中起作用。这显然使其不适合用于药理学用途。一种稳定的类似物普兰林肽已被开发出来,它具有与天然肽相似的作用、药代动力学和药效学特性。普兰林肽给药的疗效和安全性已在大量临床试验中得到测试。大约5000名接受胰岛素治疗的患者接受了普兰林肽治疗,其中约250人接受治疗≥2年。本综述的目的是:1)简要描述在动物和人体模型中所证实的胰淀素的作用;2)主要综述胰淀素类似物普兰林肽的临床试验结果。

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