Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 10, 2015; 6(15): 1285-1295
Published online Nov 10, 2015. doi: 10.4239/wjd.v6.i15.1285
New perspectives on exploitation of incretin peptides for the treatment of diabetes and related disorders
Nigel Irwin, Peter R Flatt
Nigel Irwin, Peter R Flatt, SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine BT52 1SA, Northern Ireland, United Kingdom
Author contributions: All authors contributed to the manuscript.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Nigel Irwin, SAAD Centre for Pharmacy and Diabetes, University of Ulster, Cromore Road, Coleraine BT52 1SA, Northern Ireland, United Kingdom. n.irwin@ulster.ac.uk
Telephone: +44-28-70324574 Fax: +44-28-70323939
Received: May 20, 2015
Peer-review started: May 21, 2015
First decision: September 17, 2015
Revised: September 25, 2015
Accepted: October 20, 2015
Article in press: October 27, 2015
Published online: November 10, 2015
Abstract

The applicability of stable gut hormones for the treatment of obesity-related diabetes is now undisputable. This is based predominantly on prominent and sustained glucose-lowering actions, plus evidence that these peptides can augment insulin secretion and pancreatic islet function over time. This review highlights the therapeutic potential of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), oxyntomodulin (OXM) and cholecystokinin (CCK) for obesity-related diabetes. Stable GLP-1 mimetics have already been successfully adopted into the diabetic clinic, whereas GIP, CCK and OXM molecules offer promise as potential new classes of antidiabetic drugs. Moreover, recent studies have shown improved therapeutic effects following simultaneous modulation of multiple receptor signalling pathways by combination therapy or use of dual/triple agonist peptides. However, timing and composition of injections may be important to permit interludes of beta-cell rest. The review also addresses the possible perils of incretin based drugs for treatment of prediabetes. Finally, the unanticipated utility of stable gut peptides as effective treatments for complications of diabetes, bone disorders, cognitive impairment and cardiovascular dysfunction is considered.

Keywords: Diabetes, Obesity, Incretin, Prediabetes, Gut hormones

Core tip: Stable gut hormones have well defined therapeutic actions for type 2 diabetes mellitus. In addition, simultaneous modulation of gut hormone receptors could increase therapeutic efficacy, but timing and receptor activation profile may be important. Finally, gut-derived peptides could possess benefits for bone disorders, cognitive impairment and cardiovascular dysfunction.