Imperial College London
Alternate

Professor Sir Steve Bloom FMedSci, FRS

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Departmental Academic REF2014 Lead
 
 
 
//

Contact

 

+44 (0)20 7594 9048s.bloom Website

 
 
//

Assistant

 

Ms Keda Price-Cousins +44 (0)20 7594 9048

 
//

Location

 

6N3Commonwealth BuildingHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Price:2015:10.1016/j.curtheres.2015.10.003,
author = {Price, S and Minnion, J and Bloom, SR},
doi = {10.1016/j.curtheres.2015.10.003},
journal = {Current Therapeutic Research - Clinical and Experimental},
pages = {111--115},
title = {Investigating the glucagon receptor and GLP-1 receptor activity of Oxyntomodulin-like analogues in male Wistar rats},
url = {http://dx.doi.org/10.1016/j.curtheres.2015.10.003},
volume = {77},
year = {2015}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - AimsTo investigate the effect of Glu-3 OXM-like analogues on food intake and bodyweight in male rats.BackgroundOxyntomodulin (OXM) is a natural agonist at both the glucagon receptor (GCGr) and the glucagon-like peptide 1 receptor (GLP-1r), and peripheral administration reduces food intake and increases energy expenditure in rodents and humans. Substituting the native glutamine (Gln) at amino acid position 3 of OXM for glutamate (Glu) has previously been shown to diminish GCGr activity without affecting GLP-1r activity. The effects of Glu-3 OXM analogues have not been investigated in rats.MethodsThe effect of 2 Glu-3-substituted OXM-like analogues (eg, OXM14E3 and OXM15E3) on food intake and body weight was investigated in male Wistar rats during 6 days of daily subcutaneous (SC) administration. The effects of Glu-3 substitution on analogue binding and activity at the rat GCGr and rat GLP-1 receptor were investigated in vitro using Chinese hamster ovary or Chinese hamster lung cells.ResultsWe report the novel finding that 2 5-nmol/kg Glu-3 OXM-like analogues (OXM14E3 and OXM15E3) significantly increased rat body weight by up to 4% compared with the equivalent non-Glu-3 analogues (OXM14 and OXM15), without affecting food intake. The effect of OXM15E3 on body weight was dose–dependent. Glu-3 analogues, including Glu-3 OXM, decreased glucagon-mediated cyclic adenosine monophosphate accumulation in Chinese hamster ovary cells expressing the rat GCGr, suggesting they may be acting as antagonists.ConclusionsThe results indicate Glu-3 OXM-like analogues might not be suitable tools to investigate the mechanism of OXM analogue action in a rat model because they significantly increase body weight independent of food intake. Glu-3 OXM analogues are partial agonists at the rat GCGr and may also act as antagonists, possibly resulting in the observed increase in body weight.
AU  - Price,S
AU  - Minnion,J
AU  - Bloom,SR
DO  - 10.1016/j.curtheres.2015.10.003
EP  - 115
PY  - 2015///
SN  - 1879-0313
SP  - 111
TI  - Investigating the glucagon receptor and GLP-1 receptor activity of Oxyntomodulin-like analogues in male Wistar rats
T2  - Current Therapeutic Research - Clinical and Experimental
UR  - http://dx.doi.org/10.1016/j.curtheres.2015.10.003
UR  - http://hdl.handle.net/10044/1/28357
VL  - 77
ER  -
Download