Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes Article Swipe
Kikuko Amo-Shiinoki
,
Katsuya Tanabe
,
Yoshinobu Hoshii
,
Hiroto Matsui
,
Risa Harano
,
Tatsuya Fukuda
,
Takato Takeuchi
,
Ryotaro Bouchi
,
Tokiyo Takagi
,
Masayuki Hatanaka
,
Komei Takeda
,
Shigeru Okuya
,
Wataru Nishimura
,
Atsushi Kudo
,
Shinji Tanaka
,
Minoru Tanabe
,
Takumi Akashi
,
Tetsuya Yamada
,
Yoshihiro Ogawa
,
Eiji Ikeda
,
Hiroaki Nagano
,
Yukio Tanizawa
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.143791
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1172/jci.insight.143791
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.
Related Topics
Concepts
Islet
Diabetes mellitus
Endocrinology
Internal medicine
Chromogranin A
Type 2 diabetes
Medicine
Enteroendocrine cell
Pathophysiology
Pancreatic islets
Disease
Biology
Endocrine system
Hormone
Immunohistochemistry
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1172/jci.insight.143791
- http://insight.jci.org/articles/view/143791/files/pdf
- OA Status
- gold
- Cited By
- 51
- References
- 37
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3119033173
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3119033173Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1172/jci.insight.143791Digital Object Identifier
- Title
-
Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-01-10Full publication date if available
- Authors
-
Kikuko Amo-Shiinoki, Katsuya Tanabe, Yoshinobu Hoshii, Hiroto Matsui, Risa Harano, Tatsuya Fukuda, Takato Takeuchi, Ryotaro Bouchi, Tokiyo Takagi, Masayuki Hatanaka, Komei Takeda, Shigeru Okuya, Wataru Nishimura, Atsushi Kudo, Shinji Tanaka, Minoru Tanabe, Takumi Akashi, Tetsuya Yamada, Yoshihiro Ogawa, Eiji Ikeda, Hiroaki Nagano, Yukio TanizawaList of authors in order
- Landing page
-
https://doi.org/10.1172/jci.insight.143791Publisher landing page
- PDF URL
-
https://insight.jci.org/articles/view/143791/files/pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://insight.jci.org/articles/view/143791/files/pdfDirect OA link when available
- Concepts
-
Islet, Diabetes mellitus, Endocrinology, Internal medicine, Chromogranin A, Type 2 diabetes, Medicine, Enteroendocrine cell, Pathophysiology, Pancreatic islets, Disease, Biology, Endocrine system, Hormone, ImmunohistochemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
51Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 9, 2024: 12, 2023: 15, 2022: 7, 2021: 8Per-year citation counts (last 5 years)
- References (count)
-
37Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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