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Diabetes. 2018 Sep;67(9):1858-1866. doi: 10.2337/db17-1281. Epub 2018 Jun 26.

Loss of IDO1 Expression From Human Pancreatic β-Cells Precedes Their Destruction During the Development of Type 1 Diabetes.

Author information

1
La Jolla Institute for Allergy and Immunology, La Jolla, CA.
2
University of Perugia, Perugia, Italy.
3
Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
4
Faculty of Dentistry, University of Oslo, Oslo, Norway.
5
de Duve Institute, Brussels, Belgium.
6
Ludwig Institute for Cancer Research, Brussels, Belgium.
7
La Jolla Institute for Allergy and Immunology, La Jolla, CA matthias@lji.org.
8
Novo Nordisk Diabetes Research & Development Center, Seattle, WA.

Abstract

Indoleamine 2,3 dioxygenase-1 (IDO1) is a powerful immunoregulatory enzyme that is deficient in patients with type 1 diabetes (T1D). In this study, we present the first systematic evaluation of IDO1 expression and localization in human pancreatic tissue. Although IDO1 was constitutively expressed in β-cells from donors without diabetes, less IDO1 was expressed in insulin-containing islets from double autoantibody-positive donors and patients with recent-onset T1D, although it was virtually absent in insulin-deficient islets from donors with T1D. Scatter plot analysis suggested that IDO1 decay occurred in individuals with multiple autoantibodies, prior to β-cell demise. IDO1 impairment might therefore contribute to β-cell demise and could potentially emerge as a promising therapeutic target.

PMID:
29945890
PMCID:
PMC6110313
[Available on 2019-09-01]
DOI:
10.2337/db17-1281
[Indexed for MEDLINE]
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