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

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Version: author
Serval ID
serval:BIB_54F855CFE897
Type
Article: article from journal or magazin.
Collection
Publications
Title
Circulating IGF-I and IGFBP3 Levels Control Human Colonic Stem Cell Function and Are Disrupted in Diabetic Enteropathy.
Journal
Cell Stem Cell
Author(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
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
17
Number
4
Pages
486-498
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
06/09/2016 12:48
Last modification date
20/08/2019 15:09
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