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Alteration in glucose homeostasis and persistence of the pancreatic clock in aged mPer2(Luc) mice
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SYSNO ASEP 0492490 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Alteration in glucose homeostasis and persistence of the pancreatic clock in aged mPer2(Luc) mice Author(s) Novosadová, Zuzana (FGU-C) ORCID
Polidarová, Lenka (FGU-C) RID, ORCID
Sládek, Martin (FGU-C) RID, ORCID, SAI
Sumová, Alena (FGU-C) RID, ORCIDArticle number 11668 Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 8, Aug 3 (2018)Number of pages 11 s. Language eng - English Country GB - United Kingdom Keywords circadian clock ; pancreas ; peripheral clocks ; mPer2Luc mouse ; LL ; hyperinsulinemic hypoglycaemia Subject RIV ED - Physiology OECD category Physiology (including cytology) R&D Projects GBP304/12/G069 GA ČR - Czech Science Foundation (CSF) Institutional support FGU-C - RVO:67985823 UT WOS 000440670200031 EID SCOPUS 85051080846 DOI 10.1038/s41598-018-30225-y Annotation The physiological function of the pancreas is controlled by the circadian clock. The aim of this study was to determine whether aging-induced changes in glucose homeostasis affect properties of the circadian clock in the pancreas and/or its sensitivity to disturbances in environmental lighting conditions. mPer2(Luc) mice aged 24-26 months developed hyperinsulinemic hypoglycaemia, which was likely due to the Pclo-mediated insulin hyper-secretion and Slc2 alpha 2-mediated glucose transport impairment in the pancreas, and due to the alterations in Pp1r3c-related glycogen storage and Sgk1-related glucose transport in the liver. In the pancreatic tissue, aging affected clock gene expression only marginally, it upregulated Bmal1 and downregulated Clock expression. Whereas aging significantly impaired the circadian clock in lung explants, which were used as a control tissue, the properties of the pancreatic clock in vitro were not affected. The data suggest a non-circadian role of Bmal1 in changes of pancreatic function that occur during aging. Additionally, the pancreatic clock was more sensitive to exposure of animals to constant light conditions. These findings provide an explanation for the previously demonstrated relationship between disturbances in the circadian system and disordered glucose homeostasis, including diabetes mellitus type 2, in subjects exposed to long-term shift work. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2019
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