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Positive Effects of NPY1 Receptor Activation on Islet Structure Are Driven by Pancreatic Alpha- and Beta-Cell Transdifferentiation in Diabetic Mice

Overview of attention for article published in Frontiers in endocrinology, February 2021
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Title
Positive Effects of NPY1 Receptor Activation on Islet Structure Are Driven by Pancreatic Alpha- and Beta-Cell Transdifferentiation in Diabetic Mice
Published in
Frontiers in endocrinology, February 2021
DOI 10.3389/fendo.2021.633625
Pubmed ID
Authors

Ryan A. Lafferty, Neil Tanday, R. Charlotte Moffett, Frank Reimann, Fiona M. Gribble, Peter R. Flatt, Nigel Irwin

Abstract

Enzymatically stable and specific neuropeptide Y1 receptor (NPYR1) agonists, such as sea lamprey PYY(1-36) (SL-PYY(1-36)), are believed to improve glucose regulation in diabetes by targeting pancreatic islets. In this study, streptozotocin (STZ) diabetic transgenic GluCreERT2 ;ROSA26-eYFP and Ins1Cre/+;Rosa26-eYFP mouse models have been used to study effects of sustained NPYR1 activation on islet cell composition and alpha- and beta-cell lineage transitioning. STZ induced a particularly severe form of diabetes in Ins1Cre/+;Rosa26-eYFP mice, but twice-daily administration (25 nmol/kg) of SL-PYY(1-36) for 11 days consistently improved metabolic status. Blood glucose was decreased (p < 0.05 - p < 0.001) and both fasted plasma and pancreatic insulin significantly increased by SL-PYY(1-36). In both GluCreERT2 ;ROSA26-eYFP and Ins1Cre/+; Rosa26-eYFP mice, STZ provoked characteristic losses (p < 0.05 - p < 0.001) of islet numbers, beta-cell and pancreatic islet areas together with increases in area and central islet location of alpha-cells. With exception of alpha-cell area, these morphological changes were fully, or partially, returned to non-diabetic control levels by SL-PYY(1-36). Interestingly, STZ apparently triggered decreased (p < 0.001) alpha- to beta-cell transition in GluCreERT2 ;ROSA26-eYFP mice, together with increased loss of beta-cell identity in Ins1Cre/+;Rosa26-eYFP mice, but both effects were significantly (p < 0.001) reversed by SL-PYY(1-36). SL-PYY(1-36) also apparently reduced (p < 0.05) beta- to alpha-cell conversion in Ins1Cre/+;Rosa26-eYFP mice and glucagon expressing alpha-cells in GluCreERT2 ;ROSA26-eYFP mice. These data indicate that islet benefits of prolonged NPY1R activation, and especially restoration of beta-cell mass, are observed irrespective of diabetes status, being linked to cell lineage alterations including transdifferentiation of alpha- to beta-cells.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 2 18%
Student > Bachelor 2 18%
Researcher 1 9%
Student > Master 1 9%
Unknown 5 45%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 2 18%
Agricultural and Biological Sciences 2 18%
Medicine and Dentistry 1 9%
Unknown 6 55%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 06 March 2021.
All research outputs
#17,406,906
of 26,314,361 outputs
Outputs from Frontiers in endocrinology
#4,680
of 13,418 outputs
Outputs of similar age
#275,336
of 456,680 outputs
Outputs of similar age from Frontiers in endocrinology
#193
of 458 outputs
Altmetric has tracked 26,314,361 research outputs across all sources so far. This one is in the 31st percentile – i.e., 31% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,418 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.3. This one has gotten more attention than average, scoring higher than 59% 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 456,680 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 458 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.