Regulation of core clock genes in human islets

Stamenkovic, Jelena A., Olsson, Anders H., Nagorny, Cecilia L., Malmgren, Siri, Dekker-Nitert, Marloes, Ling, Charlotte and Mulder, Hindrik (2012) Regulation of core clock genes in human islets. Metabolism: Clinical and Experimental, 61 7: 978-985. doi:10.1016/j.metabol.2011.11.013

Author Stamenkovic, Jelena A.
Olsson, Anders H.
Nagorny, Cecilia L.
Malmgren, Siri
Dekker-Nitert, Marloes
Ling, Charlotte
Mulder, Hindrik
Title Regulation of core clock genes in human islets
Journal name Metabolism: Clinical and Experimental   Check publisher's open access policy
ISSN 0026-0495
Publication date 2012-07-01
Sub-type Article (original research)
DOI 10.1016/j.metabol.2011.11.013
Open Access Status Not Open Access
Volume 61
Issue 7
Start page 978
End page 985
Total pages 8
Place of publication Maryland Heights, MO, United States
Publisher W.B. Saunders Co.
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
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Created: Mon, 05 Nov 2012, 21:50:13 EST by Marloes Dekker on behalf of Royal Brisbane Clinical School