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Altered β-cell prohormone processing and secretion in type 1 diabetes.
Diabetes 70, 1038-1050 (2021)
Analysis of data from clinical cohorts, and more recently from human pancreatic tissue, indicates that reduced prohormone processing is an early and persistent finding in type 1 diabetes. In this article, we review the current state of knowledge regarding alterations in islet prohormone expression and processing in type 1 diabetes and consider the clinical impact of these findings. Lingering questions, including pathologic etiologies and consequences of altered prohormone expression and secretion in type 1 diabetes, and the natural history of circulating prohormone production in health and disease, are considered. Finally, key next steps required to move forward in this area are outlined, including longitudinal testing of relevant clinical populations, studies that probe the genetics of altered prohormone processing, the need for combined functional and histologic testing of human pancreatic tissues, continued interrogation of the intersection between prohormone processing and autoimmunity, and optimal approaches for analysis. Successful resolution of these questions may offer the potential to use altered prohormone processing as a biomarker to inform therapeutic strategies aimed at personalized intervention during the natural history of type 1 diabetes and as a pathogenic anchor for identification of potential disease-specific endotypes.
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Publication type
Article: Journal article
Document type
Review
Keywords
C-peptide Ratio; Islet Amyloid Polypeptide; Elevated Proinsulin; 1st-degree Relatives; Healthy Siblings; Insulin; Onset; Expression; Protein; Stress
ISSN (print) / ISBN
0012-1797
e-ISSN
1939-327X
Journal
Diabetes
Quellenangaben
Volume: 70,
Issue: 5,
Pages: 1038-1050
Publisher
American Diabetes Association
Publishing Place
Alexandria, VA.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes Research Type 1 (IDF)
Grants
Canadian Institutes of Health Research
JDRF
Leona M. & Harry B. Helmsley Charitable Trust
National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)
NIDDK
nPOD
JDRF
Leona M. & Harry B. Helmsley Charitable Trust
National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)
NIDDK
nPOD