IGFBP1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation

IGFBP1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation

There is great interest in therapeutically harnessing endogenous regenerative mechanisms to increase the number of β cells in people with diabetes. By performing whole‐genome expression profiling of zebrafish islets, we identified 11 secreted proteins that are upregulated during β‐cell regeneration....

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Main Authors: Lu, Jing, Liu, Ka‐Cheuk, Schulz, Nadja, Karampelias, Christos, Charbord, Jérémie, Hilding, Agneta, Rautio, Linn, Bertolino, Philippe, Östenson, Claes‐Göran, Brismar, Kerstin, Andersson, Olov
Format: Online
Language:English
Published: John Wiley and Sons Inc. 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116948/
id pubmed-5116948
recordtype oai_dc
spelling pubmed-51169482016-11-28 IGFBP1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation Lu, Jing Liu, Ka‐Cheuk Schulz, Nadja Karampelias, Christos Charbord, Jérémie Hilding, Agneta Rautio, Linn Bertolino, Philippe Östenson, Claes‐Göran Brismar, Kerstin Andersson, Olov Articles There is great interest in therapeutically harnessing endogenous regenerative mechanisms to increase the number of β cells in people with diabetes. By performing whole‐genome expression profiling of zebrafish islets, we identified 11 secreted proteins that are upregulated during β‐cell regeneration. We then tested the proteins' ability to potentiate β‐cell regeneration in zebrafish at supraphysiological levels. One protein, insulin‐like growth factor (Igf) binding‐protein 1 (Igfbp1), potently promoted β‐cell regeneration by potentiating α‐ to β‐cell transdifferentiation. Using various inhibitors and activators of the Igf pathway, we show that Igfbp1 exerts its regenerative effect, at least partly, by inhibiting Igf signaling. Igfbp1's effect on transdifferentiation appears conserved across species: Treating mouse and human islets with recombinant IGFBP1 in vitro increased the number of cells co‐expressing insulin and glucagon threefold. Moreover, a prospective human study showed that having high IGFBP1 levels reduces the risk of developing type‐2 diabetes by more than 85%. Thus, we identify IGFBP1 as an endogenous promoter of β‐cell regeneration and highlight its clinical importance in diabetes. John Wiley and Sons Inc. 2016-08-11 2016-09-15 /pmc/articles/PMC5116948/ /pubmed/27516442 http://dx.doi.org/10.15252/embj.201592903 Text en © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Lu, Jing
Liu, Ka‐Cheuk
Schulz, Nadja
Karampelias, Christos
Charbord, Jérémie
Hilding, Agneta
Rautio, Linn
Bertolino, Philippe
Östenson, Claes‐Göran
Brismar, Kerstin
Andersson, Olov
spellingShingle Lu, Jing
Liu, Ka‐Cheuk
Schulz, Nadja
Karampelias, Christos
Charbord, Jérémie
Hilding, Agneta
Rautio, Linn
Bertolino, Philippe
Östenson, Claes‐Göran
Brismar, Kerstin
Andersson, Olov
IGFBP1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation
author_facet Lu, Jing
Liu, Ka‐Cheuk
Schulz, Nadja
Karampelias, Christos
Charbord, Jérémie
Hilding, Agneta
Rautio, Linn
Bertolino, Philippe
Östenson, Claes‐Göran
Brismar, Kerstin
Andersson, Olov
author_sort Lu, Jing
title IGFBP1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation
title_short IGFBP1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation
title_full IGFBP1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation
title_fullStr IGFBP1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation
title_full_unstemmed IGFBP1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation
title_sort igfbp1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation
description There is great interest in therapeutically harnessing endogenous regenerative mechanisms to increase the number of β cells in people with diabetes. By performing whole‐genome expression profiling of zebrafish islets, we identified 11 secreted proteins that are upregulated during β‐cell regeneration. We then tested the proteins' ability to potentiate β‐cell regeneration in zebrafish at supraphysiological levels. One protein, insulin‐like growth factor (Igf) binding‐protein 1 (Igfbp1), potently promoted β‐cell regeneration by potentiating α‐ to β‐cell transdifferentiation. Using various inhibitors and activators of the Igf pathway, we show that Igfbp1 exerts its regenerative effect, at least partly, by inhibiting Igf signaling. Igfbp1's effect on transdifferentiation appears conserved across species: Treating mouse and human islets with recombinant IGFBP1 in vitro increased the number of cells co‐expressing insulin and glucagon threefold. Moreover, a prospective human study showed that having high IGFBP1 levels reduces the risk of developing type‐2 diabetes by more than 85%. Thus, we identify IGFBP1 as an endogenous promoter of β‐cell regeneration and highlight its clinical importance in diabetes.
publisher John Wiley and Sons Inc.
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116948/
_version_ 1613734699235016704

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