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Characterization of age‐associated alterations of islet function and structure in diabetic mutant cryptochrome 1 transgenic mice

AIMS/INTRODUCTION: In earlier reports, we described that transgenic (Tg) mice ubiquitously expressing cryptochrome1 (CRY1) with a mutation in cysteine414 (CRY1‐AP Tg mice) show an early‐onset insulin‐secretory defect of diabetes mellitus resembling human maturity‐onset diabetes of the young (MODY)....

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Autores principales: Okano, Satoshi, Hayasaka, Kiyoshi, Igarashi, Masahiko, Togashi, Yoshiyuki, Nakajima, Osamu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wiley-Blackwell 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025103/
https://www.ncbi.nlm.nih.gov/pubmed/24843691
http://dx.doi.org/10.1111/jdi.12080
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author Okano, Satoshi
Hayasaka, Kiyoshi
Igarashi, Masahiko
Togashi, Yoshiyuki
Nakajima, Osamu
author_facet Okano, Satoshi
Hayasaka, Kiyoshi
Igarashi, Masahiko
Togashi, Yoshiyuki
Nakajima, Osamu
author_sort Okano, Satoshi
collection PubMed
description AIMS/INTRODUCTION: In earlier reports, we described that transgenic (Tg) mice ubiquitously expressing cryptochrome1 (CRY1) with a mutation in cysteine414 (CRY1‐AP Tg mice) show an early‐onset insulin‐secretory defect of diabetes mellitus resembling human maturity‐onset diabetes of the young (MODY). To clarify the yet undiscovered molecular pathogenesis of diabetes mellitus in which the mutant of CRY1 is involved, we examined age‐dependent characteristics of islets of CRY1‐AP Tg mice. MATERIALS AND METHODS: Immunohistochemical analyses of islets were carried out for 2‐, 4‐ and 19‐week‐old mice. Insulin contents in the pancreas and glucose‐stimulated insulin secretion of isolated islets of mice were measured at 4 weeks. Real‐time polymerase chain reaction analyses using pancreases of mice at 4 and 21 weeks‐of‐age were carried out. RESULTS: Already at a young stage, the proliferation of β‐cells was reduced in CRY1‐AP Tg mice. Insulin contents and the levels of glucose‐stimulated insulin secretion were lower than those of wild‐type controls in CRY1‐AP Tg mice at the young stage. The expression of insulin and glucose‐sensing genes was reduced at the young stage. At the mature stage, altered distribution and hyperplasia of α‐cells were observed in the islets of CRY1‐AP Tg mice. CONCLUSIONS: Architectural abnormality in islets progressed with age in CRY1‐AP Tg mice. The reduced expression of insulin and glucose‐sensing genes, along with the lowered proliferation of β‐cells from an early stage, is a possible primary cause of early‐onset insulin‐secretory defect in CRY1‐AP Tg mice. Our results suggest that CRY1 is crucial for the maintenance of β‐cell function.
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spelling pubmed-40251032014-05-19 Characterization of age‐associated alterations of islet function and structure in diabetic mutant cryptochrome 1 transgenic mice Okano, Satoshi Hayasaka, Kiyoshi Igarashi, Masahiko Togashi, Yoshiyuki Nakajima, Osamu J Diabetes Investig Articles AIMS/INTRODUCTION: In earlier reports, we described that transgenic (Tg) mice ubiquitously expressing cryptochrome1 (CRY1) with a mutation in cysteine414 (CRY1‐AP Tg mice) show an early‐onset insulin‐secretory defect of diabetes mellitus resembling human maturity‐onset diabetes of the young (MODY). To clarify the yet undiscovered molecular pathogenesis of diabetes mellitus in which the mutant of CRY1 is involved, we examined age‐dependent characteristics of islets of CRY1‐AP Tg mice. MATERIALS AND METHODS: Immunohistochemical analyses of islets were carried out for 2‐, 4‐ and 19‐week‐old mice. Insulin contents in the pancreas and glucose‐stimulated insulin secretion of isolated islets of mice were measured at 4 weeks. Real‐time polymerase chain reaction analyses using pancreases of mice at 4 and 21 weeks‐of‐age were carried out. RESULTS: Already at a young stage, the proliferation of β‐cells was reduced in CRY1‐AP Tg mice. Insulin contents and the levels of glucose‐stimulated insulin secretion were lower than those of wild‐type controls in CRY1‐AP Tg mice at the young stage. The expression of insulin and glucose‐sensing genes was reduced at the young stage. At the mature stage, altered distribution and hyperplasia of α‐cells were observed in the islets of CRY1‐AP Tg mice. CONCLUSIONS: Architectural abnormality in islets progressed with age in CRY1‐AP Tg mice. The reduced expression of insulin and glucose‐sensing genes, along with the lowered proliferation of β‐cells from an early stage, is a possible primary cause of early‐onset insulin‐secretory defect in CRY1‐AP Tg mice. Our results suggest that CRY1 is crucial for the maintenance of β‐cell function. Wiley-Blackwell 2013-09-13 2013-04-26 /pmc/articles/PMC4025103/ /pubmed/24843691 http://dx.doi.org/10.1111/jdi.12080 Text en Copyright © 2013 Asian Association for the Study of Diabetes and Wiley Publishing Asia Pty Ltd
spellingShingle Articles
Okano, Satoshi
Hayasaka, Kiyoshi
Igarashi, Masahiko
Togashi, Yoshiyuki
Nakajima, Osamu
Characterization of age‐associated alterations of islet function and structure in diabetic mutant cryptochrome 1 transgenic mice
title Characterization of age‐associated alterations of islet function and structure in diabetic mutant cryptochrome 1 transgenic mice
title_full Characterization of age‐associated alterations of islet function and structure in diabetic mutant cryptochrome 1 transgenic mice
title_fullStr Characterization of age‐associated alterations of islet function and structure in diabetic mutant cryptochrome 1 transgenic mice
title_full_unstemmed Characterization of age‐associated alterations of islet function and structure in diabetic mutant cryptochrome 1 transgenic mice
title_short Characterization of age‐associated alterations of islet function and structure in diabetic mutant cryptochrome 1 transgenic mice
title_sort characterization of age‐associated alterations of islet function and structure in diabetic mutant cryptochrome 1 transgenic mice
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025103/
https://www.ncbi.nlm.nih.gov/pubmed/24843691
http://dx.doi.org/10.1111/jdi.12080
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