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Drotar, D.M.* ; Mojica Avila, A.K. ; Bloss, D.T.* ; Cohrs, C.M. ; Manson, C.T.* ; Posgai, A.L.* ; Williams, M.D.* ; Brusko, M.A.* ; Phelps, E.A.* ; Wasserfall, C.H.* ; Speier, S. ; Atkinson, M.A.*

Impaired islet function and normal exocrine enzyme secretion occur with low inter-regional variation in type 1 diabetes.

Cell Rep. 43:114346 (2024)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Histopathological heterogeneity in the human pancreas is well documented; however, functional evidence at the tissue level is scarce. Herein, we investigate in situ glucose-stimulated islet and carbachol-stimulated acinar cell secretion across the pancreas head (PH), body (PB), and tail (PT) regions in donors without diabetes (ND; n = 15), positive for one islet autoantibody (1AAb+; n = 7), and with type 1 diabetes (T1D; <14 months duration, n = 5). Insulin, glucagon, pancreatic amylase, lipase, and trypsinogen secretion along with 3D tissue morphometrical features are comparable across regions in ND. In T1D, insulin secretion and beta-cell volume are significantly reduced within all regions, while glucagon and enzymes are unaltered. Beta-cell volume is lower despite normal insulin secretion in 1AAb+, resulting in increased volume-adjusted insulin secretion versus ND. Islet and acinar cell secretion in 1AAb+ are consistent across the PH, PB, and PT. This study supports low inter-regional variation in pancreas slice function and, potentially, increased metabolic demand in 1AAb+.
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Publication type Article: Journal article
Document type Scientific Article
Keywords 3d Morphometry ; Cp: Immunology ; Cp: Metabolism ; Exocrine Pancreas Enzymes ; Function ; Glucagon ; Human ; Insulin ; Pancreas Regions ; Pancreas Tissue Slices ; Secretion ; Type 1 Diabetes; Adult Patients; Human Pancreas; Alpha-cell; Hypoglycemia; Onset; Autoantibodies; Pathogenesis; Responses; Glucagon; Insulin
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 43, Issue: 6, Pages: , Article Number: 114346 Supplement: ,
Publisher Cell Press
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502600-005
Grants Diabetes Research Institute Foundation
DFG Collaborative Research Centre/Transregio 127
DFG
JRDF grant
Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum Munchen at the University Clinic Carl Gustav Carus of Technische Universitat Dresden
German Ministry for Education and Research
NPOD
JDRF
Leona M. and Harry B. Helmsley Charitable Trust
National Institutes of Health (NIH)
DOI 10.1016/j.celrep.2024.114346
WOS ID 001252587900001
Scopus ID 85195268399
PubMed ID 38850534
Erfassungsdatum 2024-07-19
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