Impaired islet function and normal exocrine enzyme secretion occur with low inter-regional variation in type 1 diabetes
Denise M. Drotar,
Ana Karen Mojica-Avila,
Drew T. Bloss,
Christian M. Cohrs,
Cameron T. Manson,
Amanda L. Posgai,
MacKenzie D. Williams,
Maigan A. Brusko,
Edward A. Phelps,
Clive H. Wasserfall,
Stephan Speier,
Mark A. Atkinson
Affiliations
Denise M. Drotar
Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA
Ana Karen Mojica-Avila
Institute of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD), München, Neuherberg, Germany
Drew T. Bloss
Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA
Christian M. Cohrs
Institute of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD), München, Neuherberg, Germany
Cameron T. Manson
Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA
Amanda L. Posgai
Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA
MacKenzie D. Williams
Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA
Maigan A. Brusko
Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA
Edward A. Phelps
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA
Clive H. Wasserfall
Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA; Department of Pediatrics, College of Medicine, University of Florida Diabetes Institute, Gainesville, FL, USA
Stephan Speier
Institute of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden (PLID) of the Helmholtz Zentrum München at the University Clinic Carl Gustav Carus of Technische Universität Dresden, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD), München, Neuherberg, Germany
Mark A. Atkinson
Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL 32610, USA; Department of Pediatrics, College of Medicine, University of Florida Diabetes Institute, Gainesville, FL, USA; Corresponding author
Summary: 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+.
