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Histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes

INTRODUCTION: Despite a reduced function and volume of the exocrine pancreas in type 1 diabetes, the acinar cells remain understudied in type 1 diabetes research. The hypothesis of this study is that the acinar tissue is altered in subjects with type 1 diabetes compared with subjects without diabete...

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Autores principales: Granlund, Louise, Hedin, Anders, Wahlhütter, Miriam, Seiron, Peter, Korsgren, Olle, Skog, Oskar, Lundberg, Marcus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149357/
https://www.ncbi.nlm.nih.gov/pubmed/34031141
http://dx.doi.org/10.1136/bmjdrc-2020-002076
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author Granlund, Louise
Hedin, Anders
Wahlhütter, Miriam
Seiron, Peter
Korsgren, Olle
Skog, Oskar
Lundberg, Marcus
author_facet Granlund, Louise
Hedin, Anders
Wahlhütter, Miriam
Seiron, Peter
Korsgren, Olle
Skog, Oskar
Lundberg, Marcus
author_sort Granlund, Louise
collection PubMed
description INTRODUCTION: Despite a reduced function and volume of the exocrine pancreas in type 1 diabetes, the acinar cells remain understudied in type 1 diabetes research. The hypothesis of this study is that the acinar tissue is altered in subjects with type 1 diabetes compared with subjects without diabetes. RESEARCH DESIGN AND METHODS: The cell density, expression of digestive enzymes, and transcriptome of acinar tissue at varying distances from islets were analyzed using histology, immunostaining, and AmpliSeq RNA sequencing of laser capture microdissected tissue. Pancreases examined were from organ donors with or without type 1 diabetes. RESULTS: We demonstrate preserved acinar nuclei density and find no support of acinar atrophy in type 1 diabetes. Staining for digestive enzymes (amylase, lipase, and trypsin) demonstrated an evenly distributed expression in the exocrine parenchyma; although occasional amylase-negative regions appeared in tissue that had been formalin-fixed and paraffin-embedded, this phenomenon was not evident in frozen tissue. Gene set enrichment analysis of whole transcriptome data identified transcriptional alterations in type 1 diabetes that were present in the acinar tissue independent of the distance from islets. Among these, the two most enriched gene sets were Myc Targets V2 and Estrogen Response Early. CONCLUSION: Taken together, these new data emphasize the involvement of the entire pancreas in type 1 diabetes pathology. The alteration of the gene sets Myc Targets V2 and Estrogen Response Early is a possible link to the increased incidence of pancreatic cancer in type 1 diabetes.
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spelling pubmed-81493572021-06-09 Histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes Granlund, Louise Hedin, Anders Wahlhütter, Miriam Seiron, Peter Korsgren, Olle Skog, Oskar Lundberg, Marcus BMJ Open Diabetes Res Care Pathophysiology/Complications INTRODUCTION: Despite a reduced function and volume of the exocrine pancreas in type 1 diabetes, the acinar cells remain understudied in type 1 diabetes research. The hypothesis of this study is that the acinar tissue is altered in subjects with type 1 diabetes compared with subjects without diabetes. RESEARCH DESIGN AND METHODS: The cell density, expression of digestive enzymes, and transcriptome of acinar tissue at varying distances from islets were analyzed using histology, immunostaining, and AmpliSeq RNA sequencing of laser capture microdissected tissue. Pancreases examined were from organ donors with or without type 1 diabetes. RESULTS: We demonstrate preserved acinar nuclei density and find no support of acinar atrophy in type 1 diabetes. Staining for digestive enzymes (amylase, lipase, and trypsin) demonstrated an evenly distributed expression in the exocrine parenchyma; although occasional amylase-negative regions appeared in tissue that had been formalin-fixed and paraffin-embedded, this phenomenon was not evident in frozen tissue. Gene set enrichment analysis of whole transcriptome data identified transcriptional alterations in type 1 diabetes that were present in the acinar tissue independent of the distance from islets. Among these, the two most enriched gene sets were Myc Targets V2 and Estrogen Response Early. CONCLUSION: Taken together, these new data emphasize the involvement of the entire pancreas in type 1 diabetes pathology. The alteration of the gene sets Myc Targets V2 and Estrogen Response Early is a possible link to the increased incidence of pancreatic cancer in type 1 diabetes. BMJ Publishing Group 2021-05-23 /pmc/articles/PMC8149357/ /pubmed/34031141 http://dx.doi.org/10.1136/bmjdrc-2020-002076 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
spellingShingle Pathophysiology/Complications
Granlund, Louise
Hedin, Anders
Wahlhütter, Miriam
Seiron, Peter
Korsgren, Olle
Skog, Oskar
Lundberg, Marcus
Histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes
title Histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes
title_full Histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes
title_fullStr Histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes
title_full_unstemmed Histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes
title_short Histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes
title_sort histological and transcriptional characterization of the pancreatic acinar tissue in type 1 diabetes
topic Pathophysiology/Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149357/
https://www.ncbi.nlm.nih.gov/pubmed/34031141
http://dx.doi.org/10.1136/bmjdrc-2020-002076
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