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Rodriguez-Calvo, T. ; Chen, Y.C.* ; Verchere, C.B.* ; Haataja, L.* ; Arvan, P.* ; Leete, P.* ; Richardson, S.J.* ; Morgan, N.G.* ; Qian, W.J.* ; Pugliese, A.* ; Atkinson, M.* ; Evans-Molina, C.* ; Sims, E.K.*

Altered β-cell prohormone processing and secretion in type 1 diabetes.

Diabetes 70, 1038-1050 (2021)
Postprint DOI
Open Access Green
Free by publisher: Publ. Version/Full Text online available 06/2022
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 Article Number: , Supplement: ,
Publisher American Diabetes Association
Publishing Place Alexandria, VA.
Reviewing status Peer reviewed
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