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Differential hypoglycaemic, anorectic, autonomic and emetic effects of the glucagon-like peptide receptor agonist, exendin-4, in the conscious telemetered ferret

Overview of attention for article published in Journal of Translational Medicine, December 2014
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  • Good Attention Score compared to outputs of the same age (72nd percentile)
  • Good Attention Score compared to outputs of the same age and source (77th percentile)

Mentioned by

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1 tweeter
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1 patent

Citations

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7 Dimensions

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16 Mendeley
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Title
Differential hypoglycaemic, anorectic, autonomic and emetic effects of the glucagon-like peptide receptor agonist, exendin-4, in the conscious telemetered ferret
Published in
Journal of Translational Medicine, December 2014
DOI 10.1186/s12967-014-0327-6
Pubmed ID
Authors

Zengbing Lu, Nathalie Percie Du Sert, Sze Wa Chan, Chi-Kong Yeung, Ge Lin, David TW Yew, Paul LR Andrews, John A Rudd

Abstract

BackgroundRodents are incapable of emesis and consequently the emetic potential of glucagon-like peptide-1 receptor (GLP-1R) agonists in studies designed to assess a potential blood glucose lowering action of the compound was missed. Therefore, we investigated if the ferret, a carnivore with demonstrated translation capability in emesis research, would identify the emetic potential of the GLP-1R agonist, exendin-4, and any associated effects on gastric motor function, appetite and cardiovascular homeostasis.MethodsThe biological activity of the GLP-1R ligands was investigated in vivo using a glucose tolerance test in pentobarbitone-anesthetised ferrets and in vitro using organ bath studies. Radiotelemetry was used to investigate the effect of exendin-4 on gastric myoelectric activity (GMA) and cardiovascular function in conscious ferrets; behaviour was also simultaneously assessed. Western blot was used to characterize GLP-1R distribution in the gastrointestinal and brain tissues.ResultsIn anesthetised ferrets, exendin-4 (30 nmol/kg, s.c.) reduced experimentally elevated blood glucose levels by 36.3%, whereas the GLP-1R antagonist, exendin (9¿39) (300 nmol/kg, s.c.) antagonised the effect and increased AUC0¿120 by 31.0% when injected alone (P < 0.05). In animals with radiotelemetry devices, exendin-4 (100 nmol/kg, s.c.) induced emesis in 1/9 ferrets, but inhibited food intake and decreased heart rate variability (HRV) in all animals (P < 0.05). In the animal not exhibiting emesis, there was no effect on GMA, mean arterial blood pressure, heart rate, or core body temperature. In the ferret exhibiting emesis, there was a shift in the GMA towards bradygastria with a decrease in power, and a concomitant decrease in HRV. Western blot revealed GLP-1R throughout the gastrointestinal tract but exendin-4 (up to 300 nM) and exendin (9¿39), failed to contract or relax isolated ferret gut tissues. GLP-1R were found in all major brain regions and the levels were comparable those in the vagus nerve.ConclusionsPeripherally administered exendin-4 reduced blood glucose and inhibited feeding with a low emetic potential similar to that in humans (11% vs 12.8%). A disrupted GMA only occurred in the animal exhibiting emesis raising the possibility that disruption of the GMA may influence the probability of emesis occurring in response to treatment with GLP-1R agonists.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 16 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 4 25%
Student > Postgraduate 3 19%
Student > Master 2 13%
Student > Ph. D. Student 1 6%
Researcher 1 6%
Other 2 13%
Unknown 3 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 5 31%
Nursing and Health Professions 3 19%
Medicine and Dentistry 2 13%
Psychology 2 13%
Sports and Recreations 1 6%
Other 1 6%
Unknown 2 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 April 2018.
All research outputs
#3,644,043
of 12,852,852 outputs
Outputs from Journal of Translational Medicine
#588
of 2,537 outputs
Outputs of similar age
#78,104
of 293,440 outputs
Outputs of similar age from Journal of Translational Medicine
#53
of 237 outputs
Altmetric has tracked 12,852,852 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 2,537 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has done well, scoring higher than 75% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 293,440 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 237 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.