Gut hormone polyagonists for the treatment of type 2 diabetes

被引：92

作者：

Brandt, Sara J. ^{[1
]}

Goetz, Anna ^{[1
,2
,3
]}

Tschoep, Matthias H. ^{[1
,4
,5
]}

Mueller, Timo D. ^{[1
,4
]}

机构：

[1] German Res Ctr Environm Hlth GmbH, Inst Diabet & Obes, Helmholtz Diabet Ctr, Helmholtz Zentrum Munchen, Business Campus Garching,Parkring 13, D-85748 Garching, Germany

[2] Univ Hosp RWTH Aachen, Dept Internal Med 1, Aachen, Germany

[3] German Res Ctr Environm Hlth GmbH, Inst Diabet & Regenerat, Helmholtz Diabet Ctr, Helmholtz Zentrum Munchen, Business Campus Garching,Parkring 13, D-85748 Garching, Germany

[4] German Ctr Diabet Res DZD, Neuherberg, Germany

[5] Tech Univ Munich, Div Metab Dis, Dept Med, Munich, Germany

来源：

PEPTIDES | 2018年 / 100卷

基金：

欧洲研究理事会;

关键词：

GLP-1/Glucagon Co-agonism; Polypharmacology; Type; 2; diabetes; Gip; DEPENDENT INSULINOTROPIC POLYPEPTIDE; GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; TERM WEIGHT CONTROL; GLP-1 RECEPTOR AGONISTS; PROHORMONE CONVERTASE PC2; PANCREATIC BETA-CELLS; FED HIGH-FAT; GIP RECEPTOR; BODY-WEIGHT;

D O I：

10.1016/j.peptides.2017.12.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Chemical derivatives of the gut-derived peptide hormone glucagon-like peptide 1 (GLP-1) are among the best-in-class pharmacotherapies to treat obesity and type 2 diabetes. However, GLP-1 analogs have modest weight lowering capacity, in the range of 5-10%, and the therapeutic window is hampered by dose-dependent side effects. Over the last few years, a new concept has emerged: combining the beneficial effects of several key metabolic hormones into a single molecular entity. Several unimolecular GLP-1-based polyagonists have shown superior metabolic action compared to GLP-1 monotherapies. In this review article, we highlight the history of polyagonists targeting the receptors for GLP-1, GIP and glucagon, and discuss recent progress in expanding of this concept to now allow targeted delivery of nuclear hormones via GLP-1 and other gut hormones, as a novel approach towards more personalized pharmacotherapies.

引用

页码：190 / 201

页数：12

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