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A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents

Overview of attention for article published in Nature Medicine, December 2014
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Citations

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Title
A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents
Published in
Nature Medicine, December 2014
DOI 10.1038/nm.3761
Pubmed ID
Authors

Brian Finan, Bin Yang, Nickki Ottaway, David L Smiley, Tao Ma, Christoffer Clemmensen, Joe Chabenne, Lianshan Zhang, Kirk M Habegger, Katrin Fischer, Jonathan E Campbell, Darleen Sandoval, Randy J Seeley, Konrad Bleicher, Sabine Uhles, William Riboulet, Jürgen Funk, Cornelia Hertel, Sara Belli, Elena Sebokova, Karin Conde-Knape, Anish Konkar, Daniel J Drucker, Vasily Gelfanov, Paul T Pfluger, Timo D Müller, Diego Perez-Tilve, Richard D DiMarchi, Matthias H Tschöp

Abstract

We report the discovery of a new monomeric peptide that reduces body weight and diabetic complications in rodent models of obesity by acting as an agonist at three key metabolically-related peptide hormone receptors: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptors. This triple agonist demonstrates supraphysiological potency and equally aligned constituent activities at each receptor, all without cross-reactivity at other related receptors. Such balanced unimolecular triple agonism proved superior to any existing dual coagonists and best-in-class monoagonists to reduce body weight, enhance glycemic control and reverse hepatic steatosis in relevant rodent models. Various loss-of-function models, including genetic knockout, pharmacological blockade and selective chemical knockout, confirmed contributions of each constituent activity in vivo. We demonstrate that these individual constituent activities harmonize to govern the overall metabolic efficacy, which predominantly results from synergistic glucagon action to increase energy expenditure, GLP-1 action to reduce caloric intake and improve glucose control, and GIP action to potentiate the incretin effect and buffer against the diabetogenic effect of inherent glucagon activity. These preclinical studies suggest that, so far, this unimolecular, polypharmaceutical strategy has potential to be the most effective pharmacological approach to reversing obesity and related metabolic disorders.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 246 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 5 2%
Japan 4 2%
Denmark 2 <1%
Mexico 1 <1%
United Kingdom 1 <1%
Italy 1 <1%
Switzerland 1 <1%
Germany 1 <1%
Korea, Republic of 1 <1%
Other 1 <1%
Unknown 228 93%

Demographic breakdown

Readers by professional status Count As %
Researcher 63 26%
Student > Ph. D. Student 48 20%
Other 21 9%
Student > Master 20 8%
Student > Bachelor 18 7%
Other 76 31%
Readers by discipline Count As %
Agricultural and Biological Sciences 70 28%
Medicine and Dentistry 65 26%
Biochemistry, Genetics and Molecular Biology 36 15%
Unspecified 25 10%
Pharmacology, Toxicology and Pharmaceutical Science 16 7%
Other 34 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 197. 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 02 October 2018.
All research outputs
#62,620
of 12,979,723 outputs
Outputs from Nature Medicine
#194
of 6,536 outputs
Outputs of similar age
#1,387
of 294,226 outputs
Outputs of similar age from Nature Medicine
#2
of 84 outputs
Altmetric has tracked 12,979,723 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 6,536 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 32.9. This one has done particularly well, scoring higher than 97% 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 294,226 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 84 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.