Circulating IGF-I and IGFBP3 Levels Control Human Colonic Stem Cell Function and Are Disrupted in Diabetic Enteropathy.

Détails

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Etat: Supprimée
Version: de l'auteur
ID Serval
serval:BIB_54F855CFE897
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Circulating IGF-I and IGFBP3 Levels Control Human Colonic Stem Cell Function and Are Disrupted in Diabetic Enteropathy.
Périodique
Cell Stem Cell
Auteur(s)
D'Addio F., La Rosa S., Maestroni A., Jung P., Orsenigo E., Ben Nasr M., Tezza S., Bassi R., Finzi G., Marando A., Vergani A., Frego R., Albarello L., Andolfo A., Manuguerra R., Viale E., Staudacher C., Corradi D., Batlle E., Breault D., Secchi A., Folli F., Fiorina P.
ISSN
1875-9777 (Electronic)
ISSN-L
1875-9777
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
17
Numéro
4
Pages
486-498
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
The role of circulating factors in regulating colonic stem cells (CoSCs) and colonic epithelial homeostasis is unclear. Individuals with long-standing type 1 diabetes (T1D) frequently have intestinal symptoms, termed diabetic enteropathy (DE), though its etiology is unknown. Here, we report that T1D patients with DE exhibit abnormalities in their intestinal mucosa and CoSCs, which fail to generate in vitro mini-guts. Proteomic profiling of T1D+DE patient serum revealed altered levels of insulin-like growth factor 1 (IGF-I) and its binding protein 3 (IGFBP3). IGFBP3 prevented in vitro growth of patient-derived organoids via binding its receptor TMEM219, in an IGF-I-independent manner, and disrupted in vivo CoSC function in a preclinical DE model. Restoration of normoglycemia in patients with long-standing T1D via kidney-pancreas transplantation or in diabetic mice by treatment with an ecto-TMEM219 recombinant protein normalized circulating IGF-I/IGFBP3 levels and reestablished CoSC homeostasis. These findings demonstrate that peripheral IGF-I/IGFBP3 controls CoSCs and their dysfunction in DE.
Mots-clé
Animals, Colon/cytology, Colon/physiology, Diabetes Complications/metabolism, Diabetes Complications/pathology, Diabetes Mellitus, Experimental/metabolism, Diabetes Mellitus, Experimental/pathology, Humans, Insulin-Like Growth Factor Binding Protein 3/blood, Insulin-Like Growth Factor I/metabolism, Intestinal Mucosa/metabolism, Intestinal Mucosa/pathology, Membrane Proteins/metabolism, Mice, Proteomics, Stem Cells/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/09/2016 11:48
Dernière modification de la notice
20/08/2019 14:09
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