Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes

Autor: Tetsuya Yamada, Tatsuya Fukuda, Yoshinobu Hoshii, Ryotaro Bouchi, Takato Takeuchi, Yukio Tanizawa, Shigeru Okuya, Shinji Tanaka, Hiroaki Nagano, Tokiyo Takagi, Katsuya Tanabe, Takumi Akashi, Masayuki Hatanaka, Komei Takeda, Yoshihiro Ogawa, Kikuko Amo-Shiinoki, Wataru Nishimura, Minoru Tanabe, Eiji Ikeda, Risa Harano, Hiroto Matsui, Atsushi Kudo
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
medicine.medical_treatment
Cell
Enteroendocrine cell
Type 2 diabetes
0302 clinical medicine
Endocrinology
Insulin-Secreting Cells
Insulin
Aged
80 and over
geography.geographical_feature_category
biology
Diabetes
Age Factors
Chromogranin A
General Medicine
Middle Aged
Islet
Pancreas
Exocrine
medicine.anatomical_structure
030220 oncology & carcinogenesis
Disease Progression
Medicine
Female
Research Article
Adult
medicine.medical_specialty
endocrine system
Glucagon
Islets of Langerhans
03 medical and health sciences
Diabetes mellitus
Internal medicine
medicine
Humans
Aged
geography
business.industry
Beta cells
Cell Dedifferentiation
medicine.disease
030104 developmental biology
Metabolism
Diabetes Mellitus
Type 2
Glucagon-Secreting Cells
Case-Control Studies
biology.protein
business
Zdroj: JCI Insight, Vol 6, Iss 1 (2021)
JCI Insight
ISSN: 2379-3708
Popis: 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.
Islet remodeling with dedifferentiation is a pathologic mechanism of β celldysfunction and lost during the course of progression in human type 2 diabetes.
Databáze: OpenAIRE
Externí odkaz: