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Panzer, J.K. ; Hiller, H.* ; Cohrs, C.M. ; Almaça, J.* ; Enos, S.J. ; Beery, M.* ; Cechin, S.* ; Drotar, D.M. ; Weitz, J.R.* ; Santini, J.* ; Huber, M.K.* ; Muhammad Fahd Qadir, M.* ; Pastori, R.L.* ; Domínguez-Bendala, J.* ; Phelps, E.A.* ; Atkinson, M.A.* ; Pugliese, A.* ; Caicedo, A.* ; Kusmartseva, I.* ; Speier, S.

Pancreas tissue slices from organ donors enable in situ analysis of type 1 diabetes pathogenesis.

JCI insight 5:134525 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
In type 1 diabetes (T1D), autoimmune destruction of pancreatic beta cells leads to insulin deficiency and loss of glycemic control. However, knowledge about human pancreas pathophysiology in T1D remains incomplete. To address this limitation, we established a pancreas tissue slice platform of donor organs with and without diabetes, facilitating the first live cell studies of human pancreas in T1D pathogenesis to our knowledge. We show that pancreas tissue slices from organ donors allow thorough assessment of processes critical for disease development, including insulin secretion, beta cell physiology, endocrine cell morphology, and immune infiltration within the same donor organ. Using this approach, we compared detailed pathophysiological profiles for 4 pancreata from donors with T1D with 19 nondiabetic control donors. We demonstrate that cell loss, beta cell dysfunction, alterations of beta cell physiology, and islet infiltration contributed differently to individual cases of T1D, allowing insight into pathophysiology and heterogeneity of T1D pathogenesis. Thus, our study demonstrates that organ donor pancreas tissue slices represent a promising and potentially novel approach in the search for successful prevention and reversal strategies of T1D.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Autoimmune Diseases ; Autoimmunity ; Beta Cells ; Diabetes ; Endocrinology; Alpha-cell-function; Nod Mouse Model; Animal-models; Beta-cells; Islet; Onset; Morphology; Expression; Langerhans; Insulitis
ISSN (print) / ISBN 2379-3708
e-ISSN 2379-3708
Journal JCI insight
Quellenangaben Volume: 5, Issue: 8, Pages: , Article Number: 134525 Supplement: ,
Publisher Clarivate
Publishing Place Ann Arbor, Michigan
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)