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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)

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	Open Access Gold

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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

Corresponding Author

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)