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Regulation of core clock genes in human islets.

Stamenkovic, Jelena LU ; Olsson, Anders H LU ; Nagorny, Cecilia LU ; Malmgren, Siri LU ; Dekker Nitert, Marloes LU ; Ling, Charlotte LU and Mulder, Hindrik LU (2012) In Metabolism, Clinical and Experimental 61(7). p.978-985
Abstract
Nearly all mammalian cells express a set of genes known as clock genes. These regulate the circadian rhythm of cellular processes by means of negative and positive autoregulatory feedback loops of transcription and translation. Recent genomewide association studies have demonstrated an association between a polymorphism near the circadian clock gene CRY2 and elevated fasting glucose. To determine whether clock genes could play a pathogenetic role in the disease, we examined messenger RNA (mRNA) expression of core clock genes in human islets from donors with or without type 2 diabetes mellitus. Microarray and quantitative real-time polymerase chain reaction analyses were used to assess expression of the core clock genes CLOCK, BMAL-1, PER1... (More)
Nearly all mammalian cells express a set of genes known as clock genes. These regulate the circadian rhythm of cellular processes by means of negative and positive autoregulatory feedback loops of transcription and translation. Recent genomewide association studies have demonstrated an association between a polymorphism near the circadian clock gene CRY2 and elevated fasting glucose. To determine whether clock genes could play a pathogenetic role in the disease, we examined messenger RNA (mRNA) expression of core clock genes in human islets from donors with or without type 2 diabetes mellitus. Microarray and quantitative real-time polymerase chain reaction analyses were used to assess expression of the core clock genes CLOCK, BMAL-1, PER1 to 3, and CRY1 and 2 in human islets. Insulin secretion and insulin content in human islets were measured by radioimmunoassay. The mRNA levels of PER2, PER3, and CRY2 were significantly lower in islets from donors with type 2 diabetes mellitus. To investigate the functional relevance of these clock genes, we correlated their expression to insulin content and glycated hemoglobin levels: mRNA levels of PER2 (ρ = 0.33, P = .012), PER3 (ρ = 0.30, P = .023), and CRY2 (ρ = 0.37, P = .0047) correlated positively with insulin content. Of these genes, expression of PER3 and CRY2 correlated negatively with glycated hemoglobin levels (ρ = -0.44, P = .0012; ρ = -0.28, P = .042). Furthermore, in an in vitro model mimicking pathogenetic conditions, the PER3 mRNA level was reduced in human islets exposed to 16.7 mmol/L glucose per 1 mmol/L palmitate for 48 hours (P = .003). Core clock genes are regulated in human islets. The data suggest that perturbations of circadian clock components may contribute to islet pathophysiology in human type 2 diabetes mellitus. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Metabolism, Clinical and Experimental
volume
61
issue
7
pages
978 - 985
publisher
Elsevier
external identifiers
  • wos:000305371700010
  • pmid:22304835
  • scopus:84862152416
ISSN
1532-8600
DOI
10.1016/j.metabol.2011.11.013
language
English
LU publication?
yes
id
f51574e5-ef68-45b4-b3c3-ffda8524a798 (old id 2367301)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22304835?dopt=Abstract
date added to LUP
2012-03-02 08:59:36
date last changed
2017-10-22 03:59:10
@article{f51574e5-ef68-45b4-b3c3-ffda8524a798,
  abstract     = {Nearly all mammalian cells express a set of genes known as clock genes. These regulate the circadian rhythm of cellular processes by means of negative and positive autoregulatory feedback loops of transcription and translation. Recent genomewide association studies have demonstrated an association between a polymorphism near the circadian clock gene CRY2 and elevated fasting glucose. To determine whether clock genes could play a pathogenetic role in the disease, we examined messenger RNA (mRNA) expression of core clock genes in human islets from donors with or without type 2 diabetes mellitus. Microarray and quantitative real-time polymerase chain reaction analyses were used to assess expression of the core clock genes CLOCK, BMAL-1, PER1 to 3, and CRY1 and 2 in human islets. Insulin secretion and insulin content in human islets were measured by radioimmunoassay. The mRNA levels of PER2, PER3, and CRY2 were significantly lower in islets from donors with type 2 diabetes mellitus. To investigate the functional relevance of these clock genes, we correlated their expression to insulin content and glycated hemoglobin levels: mRNA levels of PER2 (ρ = 0.33, P = .012), PER3 (ρ = 0.30, P = .023), and CRY2 (ρ = 0.37, P = .0047) correlated positively with insulin content. Of these genes, expression of PER3 and CRY2 correlated negatively with glycated hemoglobin levels (ρ = -0.44, P = .0012; ρ = -0.28, P = .042). Furthermore, in an in vitro model mimicking pathogenetic conditions, the PER3 mRNA level was reduced in human islets exposed to 16.7 mmol/L glucose per 1 mmol/L palmitate for 48 hours (P = .003). Core clock genes are regulated in human islets. The data suggest that perturbations of circadian clock components may contribute to islet pathophysiology in human type 2 diabetes mellitus.},
  author       = {Stamenkovic, Jelena and Olsson, Anders H and Nagorny, Cecilia and Malmgren, Siri and Dekker Nitert, Marloes and Ling, Charlotte and Mulder, Hindrik},
  issn         = {1532-8600},
  language     = {eng},
  number       = {7},
  pages        = {978--985},
  publisher    = {Elsevier},
  series       = {Metabolism, Clinical and Experimental},
  title        = {Regulation of core clock genes in human islets.},
  url          = {http://dx.doi.org/10.1016/j.metabol.2011.11.013},
  volume       = {61},
  year         = {2012},
}