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Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes
Dedifferentiation has been implicated in β cell dysfunction and loss in rodent diabetes. However, the pathophysiological significance in humans remains unclear. To elucidate this, we analyzed surgically resected pancreatic tissues of 26 Japanese subjects with diabetes and 11 nondiabetic subjects, wh...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Society for Clinical Investigation
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821596/ https://www.ncbi.nlm.nih.gov/pubmed/33427207 http://dx.doi.org/10.1172/jci.insight.143791 |
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author | Amo-Shiinoki, Kikuko Tanabe, Katsuya Hoshii, Yoshinobu Matsui, Hiroto Harano, Risa Fukuda, Tatsuya Takeuchi, Takato Bouchi, Ryotaro Takagi, Tokiyo Hatanaka, Masayuki Takeda, Komei Okuya, Shigeru Nishimura, Wataru Kudo, Atsushi Tanaka, Shinji Tanabe, Minoru Akashi, Takumi Yamada, Tetsuya Ogawa, Yoshihiro Ikeda, Eiji Nagano, Hiroaki Tanizawa, Yukio |
author_facet | Amo-Shiinoki, Kikuko Tanabe, Katsuya Hoshii, Yoshinobu Matsui, Hiroto Harano, Risa Fukuda, Tatsuya Takeuchi, Takato Bouchi, Ryotaro Takagi, Tokiyo Hatanaka, Masayuki Takeda, Komei Okuya, Shigeru Nishimura, Wataru Kudo, Atsushi Tanaka, Shinji Tanabe, Minoru Akashi, Takumi Yamada, Tetsuya Ogawa, Yoshihiro Ikeda, Eiji Nagano, Hiroaki Tanizawa, Yukio |
author_sort | Amo-Shiinoki, Kikuko |
collection | PubMed |
description | Dedifferentiation has been implicated in β cell dysfunction and loss in rodent diabetes. However, the pathophysiological significance in humans remains unclear. To elucidate this, we analyzed surgically resected pancreatic tissues of 26 Japanese subjects with diabetes and 11 nondiabetic subjects, who had been overweight during adulthood but had no family history of diabetes. The diabetic subjects were subclassified into 3 disease stage categories, early, advanced, and intermediate. Despite no numerical changes in endocrine cells immunoreactive for chromogranin A (ChgA), diabetic islets showed profound β cell loss, with an increase in α cells without an increase in insulin and glucagon double-positive cells. The proportion of dedifferentiated cells that retain ChgA immunoreactivity without 4 major islet hormones was strikingly increased in diabetic islets and rose substantially during disease progression. The increased dedifferentiated cell ratio was inversely correlated with declining C-peptide index. Moreover, a subset of islet cells converted into exocrine-like cells during disease progression. These results indicate that islet remodeling with dedifferentiation is the underlying cause of β cell failure during the course of diabetes progression in humans. |
format | Online Article Text |
id | pubmed-7821596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78215962021-01-25 Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes Amo-Shiinoki, Kikuko Tanabe, Katsuya Hoshii, Yoshinobu Matsui, Hiroto Harano, Risa Fukuda, Tatsuya Takeuchi, Takato Bouchi, Ryotaro Takagi, Tokiyo Hatanaka, Masayuki Takeda, Komei Okuya, Shigeru Nishimura, Wataru Kudo, Atsushi Tanaka, Shinji Tanabe, Minoru Akashi, Takumi Yamada, Tetsuya Ogawa, Yoshihiro Ikeda, Eiji Nagano, Hiroaki Tanizawa, Yukio JCI Insight Research Article Dedifferentiation has been implicated in β cell dysfunction and loss in rodent diabetes. However, the pathophysiological significance in humans remains unclear. To elucidate this, we analyzed surgically resected pancreatic tissues of 26 Japanese subjects with diabetes and 11 nondiabetic subjects, who had been overweight during adulthood but had no family history of diabetes. The diabetic subjects were subclassified into 3 disease stage categories, early, advanced, and intermediate. Despite no numerical changes in endocrine cells immunoreactive for chromogranin A (ChgA), diabetic islets showed profound β cell loss, with an increase in α cells without an increase in insulin and glucagon double-positive cells. The proportion of dedifferentiated cells that retain ChgA immunoreactivity without 4 major islet hormones was strikingly increased in diabetic islets and rose substantially during disease progression. The increased dedifferentiated cell ratio was inversely correlated with declining C-peptide index. Moreover, a subset of islet cells converted into exocrine-like cells during disease progression. These results indicate that islet remodeling with dedifferentiation is the underlying cause of β cell failure during the course of diabetes progression in humans. American Society for Clinical Investigation 2021-01-11 /pmc/articles/PMC7821596/ /pubmed/33427207 http://dx.doi.org/10.1172/jci.insight.143791 Text en © 2021 Amo-Shiinoki et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Amo-Shiinoki, Kikuko Tanabe, Katsuya Hoshii, Yoshinobu Matsui, Hiroto Harano, Risa Fukuda, Tatsuya Takeuchi, Takato Bouchi, Ryotaro Takagi, Tokiyo Hatanaka, Masayuki Takeda, Komei Okuya, Shigeru Nishimura, Wataru Kudo, Atsushi Tanaka, Shinji Tanabe, Minoru Akashi, Takumi Yamada, Tetsuya Ogawa, Yoshihiro Ikeda, Eiji Nagano, Hiroaki Tanizawa, Yukio Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes |
title | Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes |
title_full | Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes |
title_fullStr | Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes |
title_full_unstemmed | Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes |
title_short | Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes |
title_sort | islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821596/ https://www.ncbi.nlm.nih.gov/pubmed/33427207 http://dx.doi.org/10.1172/jci.insight.143791 |
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