Premium
IGFBP 1 increases β‐cell regeneration by promoting α‐ to β‐cell transdifferentiation
Author(s) -
Lu Jing,
Liu KaCheuk,
Schulz Nadja,
Karampelias Christos,
Charbord Jérémie,
Hilding Agneta,
Rautio Linn,
Bertolino Philippe,
Östenson ClaesGöran,
Brismar Kerstin,
Andersson Olov
Publication year - 2016
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201592903
Subject(s) - transdifferentiation , biology , zebrafish , regeneration (biology) , microbiology and biotechnology , cell , cell growth , stem cell , biochemistry , gene
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 IGFBP 1 in vitro increased the number of cells co‐expressing insulin and glucagon threefold. Moreover, a prospective human study showed that having high IGFBP 1 levels reduces the risk of developing type‐2 diabetes by more than 85%. Thus, we identify IGFBP 1 as an endogenous promoter of β‐cell regeneration and highlight its clinical importance in diabetes.