Incretin hormone mimetics and analogues in diabetes therapeutics

被引:83
作者
Green, Brian D. [1 ]
Flatt, Peter R. [2 ]
机构
[1] Queens Univ Belfast, Sch Biol Sci, Belfast BT6 0NJ, Antrim, North Ireland
[2] Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland
关键词
incretin; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; insulin; type-2; diabetes; glucose homeostasis; exendin;
D O I
10.1016/j.beem.2007.09.003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The incretin hormones glucagon-like peptide-I (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are physiological gut peptides with insulin-releasing and extrapancreatic glucoregulatory actions. Incretin analogues/mimetics activate GLP-I or GIP receptors whilst avoiding physiological inactivation by dipeptidyl peptidase 4 (DPP-4), and they represent one of the newest classes of antidiabetic drug. The first clinically approved GLP-1 mimetic for the treatment of type-2 diabetes is exenatide (Byetta/exendin) which is administered subcutaneously twice daily. Clinical trials of liraglutide, a GLP-1 analogue suitable for once-daily administration, are ongoing. A number of other incretin molecules are at earlier stages of development. This review discusses the various attributes of GLP-1 and GIP for diabetes treatment and summarises current clinical data. Additionally, it explores the therapeutic possibilities offered by preclinical agents, such as non-peptide GLP-1 mimetics, GLP-1/glucagon hybrid peptides, and specific GIP receptor antagonists.
引用
收藏
页码:497 / 516
页数:20
相关论文
共 107 条
[11]   A radioimmunoassay for LY315902, an analog of glucagon-like insulinotropic peptide, and its application in the study of canine pharmacokinetics [J].
Chou, JZ ;
Place, GD ;
Waters, DG ;
Kirkwood, JA ;
Bowsher, RR .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1997, 86 (07) :768-773
[12]   Dual-acting peptide with prolonged glucagon-like peptide-1 receptor agonist and glucagon receptor antagonist activity for the treatment of type 2 diabetes [J].
Claus, Thomas H. ;
Pan, Clark Q. ;
Buxton, Joanne M. ;
Yang, Ling ;
Reynolds, Jennifer C. ;
Barucci, Nicole ;
Burns, Michael ;
Ortiz, Astrid A. ;
Roczniak, Steve ;
Livingston, James N. ;
Clairmont, Kevin B. ;
Whelan, James P. .
JOURNAL OF ENDOCRINOLOGY, 2007, 192 (02) :371-380
[13]  
Clements RH, 2004, AM SURGEON, V70, P1
[14]   Exenatide blocks JAK1-STAT1 in pancreatic beta cells [J].
Couto, Francesca M. ;
Minn, Alexandra H. ;
Pise-Masison, Cynthia A. ;
Radonovich, Mike ;
Brady, John N. ;
Hanson, Matthew ;
Fernandez, Luis A. ;
Wang, Ping ;
Kendziorski, Christina ;
Shalev, Anath .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2007, 56 (07) :915-918
[15]  
Creutzfeldt M, 1974, Gastroenterology, V67, P748
[16]   Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients [J].
Creutzfeldt, WOC ;
Orskov, C ;
Kleine, N ;
Holst, JJ ;
Willms, B ;
Nauck, MA .
DIABETES CARE, 1996, 19 (06) :580-586
[17]   GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations [J].
Deacon, Carolyn F. ;
Plamboeck, Astrid ;
Rosenkilde, Mette M. ;
de Heer, Jocelyn ;
Holst, Jens J. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2006, 291 (03) :E468-E475
[18]   Circulation and degradation of GIP and GLP-1 [J].
Deacon, CF .
HORMONE AND METABOLIC RESEARCH, 2004, 36 (11-12) :761-765
[19]   GLP-1-(9-36) amide reduces blood glucose in anesthetized pigs by a mechanism that does not involve insulin secretion [J].
Deacon, CF ;
Plamboeck, A ;
Moller, S ;
Holst, JJ .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2002, 282 (04) :E873-E879
[20]   Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes [J].
DeFronzo, RA ;
Ratner, RE ;
Han, J ;
Kim, DD ;
Fineman, MS ;
Baron, AD .
DIABETES CARE, 2005, 28 (05) :1092-1100