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An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice

AIMS/HYPOTHESIS: Loss of circadian clocks from all tissues causes defective glucose homeostasis as well as loss of feeding and activity rhythms. Little is known about peripheral tissue clocks, so we tested the hypothesis that an intrinsic circadian clock of the pancreas is important for glucose home...

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Autores principales: Sadacca, L. A., Lamia, K. A., deLemos, A. S., Blum, B., Weitz, C. J.
Formato: Texto
Lenguaje:English
Publicado: Springer-Verlag 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995870/
https://www.ncbi.nlm.nih.gov/pubmed/20890745
http://dx.doi.org/10.1007/s00125-010-1920-8
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author Sadacca, L. A.
Lamia, K. A.
deLemos, A. S.
Blum, B.
Weitz, C. J.
author_facet Sadacca, L. A.
Lamia, K. A.
deLemos, A. S.
Blum, B.
Weitz, C. J.
author_sort Sadacca, L. A.
collection PubMed
description AIMS/HYPOTHESIS: Loss of circadian clocks from all tissues causes defective glucose homeostasis as well as loss of feeding and activity rhythms. Little is known about peripheral tissue clocks, so we tested the hypothesis that an intrinsic circadian clock of the pancreas is important for glucose homeostasis. METHODS: We monitored real-time bioluminescence of pancreas explants from circadian reporter mice and examined clock gene expression in beta cells by immunohistochemistry and in situ hybridisation. We generated mice selectively lacking the essential clock gene Bmal1 (also known as Arntl) in the pancreas and tested mutant mice and littermate controls for glucose and insulin tolerance, insulin production and behaviour. We examined islets isolated from mutants and littermate controls for glucose-stimulated insulin secretion and total insulin content. RESULTS: Pancreas explants exhibited robust circadian rhythms. Clock genes Bmal1 and Per1 were expressed in beta cells. Despite normal activity and feeding behaviour, mutant mice lacking clock function in the pancreas had severe glucose intolerance and defective insulin production; their isolated pancreatic islets had defective glucose-stimulated insulin secretion, but normal total insulin content. CONCLUSIONS/INTERPRETATION: The mouse pancreas has an autonomous clock function and beta cells are very likely to be one of the pancreatic cell types possessing an intrinsic clock. The Bmal1 circadian clock gene is required in the pancreas, probably in beta cells, for normal insulin secretion and glucose homeostasis. Our results provide evidence for a previously unrecognised molecular regulator of pancreatic glucose-sensing and/or insulin secretion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-010-1920-8) contains supplementary material, which is available to authorised users.
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spelling pubmed-29958702011-01-04 An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice Sadacca, L. A. Lamia, K. A. deLemos, A. S. Blum, B. Weitz, C. J. Diabetologia Short Communication AIMS/HYPOTHESIS: Loss of circadian clocks from all tissues causes defective glucose homeostasis as well as loss of feeding and activity rhythms. Little is known about peripheral tissue clocks, so we tested the hypothesis that an intrinsic circadian clock of the pancreas is important for glucose homeostasis. METHODS: We monitored real-time bioluminescence of pancreas explants from circadian reporter mice and examined clock gene expression in beta cells by immunohistochemistry and in situ hybridisation. We generated mice selectively lacking the essential clock gene Bmal1 (also known as Arntl) in the pancreas and tested mutant mice and littermate controls for glucose and insulin tolerance, insulin production and behaviour. We examined islets isolated from mutants and littermate controls for glucose-stimulated insulin secretion and total insulin content. RESULTS: Pancreas explants exhibited robust circadian rhythms. Clock genes Bmal1 and Per1 were expressed in beta cells. Despite normal activity and feeding behaviour, mutant mice lacking clock function in the pancreas had severe glucose intolerance and defective insulin production; their isolated pancreatic islets had defective glucose-stimulated insulin secretion, but normal total insulin content. CONCLUSIONS/INTERPRETATION: The mouse pancreas has an autonomous clock function and beta cells are very likely to be one of the pancreatic cell types possessing an intrinsic clock. The Bmal1 circadian clock gene is required in the pancreas, probably in beta cells, for normal insulin secretion and glucose homeostasis. Our results provide evidence for a previously unrecognised molecular regulator of pancreatic glucose-sensing and/or insulin secretion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-010-1920-8) contains supplementary material, which is available to authorised users. Springer-Verlag 2010-10-03 2011 /pmc/articles/PMC2995870/ /pubmed/20890745 http://dx.doi.org/10.1007/s00125-010-1920-8 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Short Communication
Sadacca, L. A.
Lamia, K. A.
deLemos, A. S.
Blum, B.
Weitz, C. J.
An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice
title An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice
title_full An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice
title_fullStr An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice
title_full_unstemmed An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice
title_short An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice
title_sort intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995870/
https://www.ncbi.nlm.nih.gov/pubmed/20890745
http://dx.doi.org/10.1007/s00125-010-1920-8
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