Impaired islet function and normal exocrine enzyme secretion occur with low inter-regional variation in type 1 diabetes
Year: 2024
Type: article
Abstract: 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+.
Source: Cell Reports
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: Diabetes Research Institute Foundation, California Department of Fish and Game, Leona M. and Harry B. Helmsley Charitable Trust, Juvenile Diabetes Research Foundation United States of America, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Technische Universität Dresden, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Nebraska Center for the Prevention of Obesity Diseases, College of Education and Human Sciences, University of Nebraska–Lincoln, JDRF
Awards: G1154828164, G3026674046, Regional and lobular heterogeneity of human pancreas morphology and function in type 1 diabetes pathogenesis, G4606767805, G5088304581, G8256389157, G8801187269, Immune Function and the Progression to Type 1 Diabetes, Co-registration of Cell Organization, Phenotype and Function in the Human Pancreas During Type 1 Diabetes
OpenAlex ID: W4399476329