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Impaired islet function and normal exocrine enzyme secretion occur with low inter-regional variation in type 1 diabetes.
Cell Rep. 43:114346 (2024)
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
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Journal
Cell Reports
Quellenangaben
Volume: 43,
Issue: 6,
Article Number: 114346
Publisher
Cell Press
Publishing Place
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute for Pancreatic Beta Cell Research (IPI)
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)
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)