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01-02-2009 | Article

Clock gene expression in peripheral leucocytes of patients with type 2 diabetes

Authors: H. Ando, T. Takamura, N. Matsuzawa-Nagata, K. R. Shima, T. Eto, H. Misu, M. Shiramoto, T. Tsuru, S. Irie, A. Fujimura, S. Kaneko

Published in: Diabetologia | Issue 2/2009

Abstract

Aim/hypothesis

Recent studies have demonstrated relationships between circadian clock function and the development of metabolic diseases such as type 2 diabetes. We investigated whether the peripheral circadian clock is impaired in patients with type 2 diabetes.

Methods

Peripheral leucocytes were obtained from eight patients with diabetes and six comparatively young non-diabetic volunteers at 09:00, 15:00, 21:00 and 03:00 hours (study 1) and from 12 male patients with diabetes and 14 age-matched men at 09:00 hours (study 2). Transcript levels of clock genes (CLOCK, BMAL1 [also known as ARNTL], PER1, PER2, PER3 and CRY1) were determined by real-time quantitative PCR.

Results

In study 1, mRNA expression patterns of BMAL1, PER1, PER2 and PER3 exhibited 24 h rhythmicity in the leucocytes of all 14 individuals. The expression levels of these mRNAs were significantly (p < 0.05) lower in patients with diabetes than in non-diabetic individuals at one or more time points. Moreover, the amplitudes of mRNA expression rhythms of PER1 and PER3 genes tended to diminish in patients with diabetes. In study 2, leucocytes obtained from patients with diabetes expressed significantly (p < 0.05) lower transcript levels of BMAL1, PER1 and PER3 compared with leucocytes from control individuals, and transcript expression was inversely correlated with HbA_1c levels (ρ = −0.47 to −0.55, p < 0.05).

Conclusions/interpretation

These results suggest that rhythmic mRNA expression of clock genes is dampened in peripheral leucocytes of patients with type 2 diabetes. The impairment of the circadian clock appears to be closely associated with the pathophysiology of type 2 diabetes in humans.

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Title: Clock gene expression in peripheral leucocytes of patients with type 2 diabetes
Authors: H. Ando
T. Takamura
N. Matsuzawa-Nagata
K. R. Shima
T. Eto
H. Misu
M. Shiramoto
T. Tsuru
S. Irie
A. Fujimura
S. Kaneko
Publication date: 01-02-2009
Publisher: Springer-Verlag
Published in: Diabetologia / Issue 2/2009
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-008-1194-6

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