PMID- 26843896
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160204
LR  - 20220131
IS  - 0011-393X (Print)
IS  - 1879-0313 (Electronic)
IS  - 0011-393X (Linking)
VI  - 77
DP  - 2015 Dec
TI  - Investigating the Glucagon Receptor and Glucagon-Like Peptide 1 Receptor Activity 
      of Oxyntomodulin-Like Analogues in Male Wistar Rats.
PG  - 111-5
LID - 10.1016/j.curtheres.2015.10.003 [doi]
AB  - AIMS: To investigate the effect of Glu-3 OXM-like analogues on food intake and 
      bodyweight in male rats. BACKGROUND: Oxyntomodulin (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. METHODS: The 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. RESULTS: We 
      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. CONCLUSIONS: The 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.
FAU - Price, Samantha L
AU  - Price SL
AD  - Department of Investigative Medicine, Imperial College London, London, United 
      Kingdom.
FAU - Minnion, James S
AU  - Minnion JS
AD  - Department of Investigative Medicine, Imperial College London, London, United 
      Kingdom.
FAU - Bloom, Stephen R
AU  - Bloom SR
AD  - Department of Investigative Medicine, Imperial College London, London, United 
      Kingdom.
LA  - eng
GR  - BB/E52708X/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - MR/J010731/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20151102
PL  - United States
TA  - Curr Ther Res Clin Exp
JT  - Current therapeutic research, clinical and experimental
JID - 0372621
PMC - PMC4701715
OTO - NOTNLM
OT  - analogue
OT  - body weight
OT  - glucagons
OT  - oxyntomodulin
EDAT- 2016/02/05 06:00
MHDA- 2016/02/05 06:01
PMCR- 2015/11/02
CRDT- 2016/02/05 06:00
PHST- 2015/10/24 00:00 [accepted]
PHST- 2016/02/05 06:00 [entrez]
PHST- 2016/02/05 06:00 [pubmed]
PHST- 2016/02/05 06:01 [medline]
PHST- 2015/11/02 00:00 [pmc-release]
AID - S0011-393X(15)00015-6 [pii]
AID - 10.1016/j.curtheres.2015.10.003 [doi]
PST - epublish
SO  - Curr Ther Res Clin Exp. 2015 Nov 2;77:111-5. doi: 
      10.1016/j.curtheres.2015.10.003. eCollection 2015 Dec.