Regulation of core clock genes in human islets

Stamenkovic, Jelena; Olsson, Anna; Nagorny, Cecilia; Malmgren, Siri; Nitert, Marloes Dekker; Ling, Charlotte; Mulder, Hindrik

doi:10.1016/j.metabol.2011.11.013

Cited by 86 publications

(60 citation statements)

References 20 publications

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“…This study found that the peak levels of serum concentrations of the markers occurred in the early evening, suggesting a correlation between oxidative damage and increased metabolism. The significance of rhythmic factors in diabetes was also shown in a study that looked at mRNA expression of the core clock genes in cells isolated from patients with and without type 2 diabetes, in addition to insulin secretion (167). The authors found that PER2, PER3, and CRY2 mRNA levels in human islets were significantly lower in patients with type II diabetes than in normal controls.…”

Section: Diabetesmentioning

confidence: 87%

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

Wilking

Ndiaye²,

Mukhtar³

et al. 2013

Antioxidants & Redox Signaling

238

192

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Significance: Oxygen and circadian rhythmicity are essential in a myriad of physiological processes to maintain homeostasis, from blood pressure and sleep/wake cycles, down to cellular signaling pathways that play critical roles in health and disease. If the human body or cells experience significant stress, their ability to regulate internal systems, including redox levels and circadian rhythms, may become impaired. At cellular as well as organismal levels, impairment in redox regulation and circadian rhythms may lead to a number of adverse effects, including the manifestation of a variety of diseases such as heart diseases, neurodegenerative conditions, and cancer. Recent Advances: Researchers have come to an understanding as to the basics of the circadian rhythm mechanism, as well as the importance of the numerous species of oxidative stress components. The effects of oxidative stress and dysregulated circadian rhythms have been a subject of intense investigations since they were first discovered, and recent investigations into the molecular mechanisms linking the two have started to elucidate the bases of their connection. Critical Issues: While much is known about the mechanics and importance of oxidative stress systems and circadian rhythms, the front where they interact has had very little research focused on it. This review discusses the idea that these two systems are together intricately involved in the healthy body, as well as in disease. Future Directions: We believe that for a more efficacious management of diseases that have both circadian rhythm and oxidative stress components in their pathogenesis, targeting both systems in tandem would be far more successful.

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Section: Diabetesmentioning

confidence: 87%

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

Wilking

Ndiaye²,

Mukhtar³

et al. 2013

Antioxidants & Redox Signaling

238

192

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“…The MTNR1B variant is an established locus associated with type 2 diabetes, and variants at CRY2 have been tentatively associated with type 2 diabetes [6]. In human islets, the expression of CRY2 mRNA has been shown to be negatively correlated with levels of glycated haemoglobin, and the expression of CRY2 mRNA was lower in participants with type 2 diabetes [7]. Several recently published studies have further indicated the importance of CRY2 and its circadian co-regulator CRY1 on glucose metabolism and energy homeostasis in mice [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Season-dependent associations of circadian rhythm-regulating loci (CRY1, CRY2 and MTNR1B) and glucose homeostasis: the GLACIER Study

et al. 2015

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Aims/hypothesis The association of single nucleotide polymorphisms (SNPs) proximal to CRY2 and MTNR1B with fasting glucose is well established. CRY1/2 and MTNR1B encode proteins that regulate circadian rhythmicity and influence energy metabolism. Here we tested whether season modified the relationship of these loci with blood glucose concentration. Methods SNPs rs8192440 (CRY1), rs11605924 (CRY2) and rs10830963 (MTNR1B) were genotyped in a prospective cohort study from northern Sweden (n=16,499). The number of hours of daylight exposure during the year ranged from 4.5 to 22 h daily. Owing to the non-linear distribution of daylight throughout the year, season was dichotomised based on the vernal and autumnal equinoxes. Effect modification was assessed using linear regression models fitted with a SNP × season interaction term, marginal effect terms and putative confounding variables, with fasting or 2 h glucose concentrations as outcomes. Results The rs8192440 (CRY1) variant was only associated with fasting glucose among participants (n=2,318) examined during the light season ( β=−0.04 mmol/l per A allele, 95% CI −0.08, −0.01, p=0.02, p interaction =0.01). In addition to the established association with fasting glucose, the rs11605924 (CRY2) and rs10830963 (MTNR1B) loci were associated with 2 h glucose concentrations ( β=0.07 mmol/l per A allele, 95% CI 0.03, 0.12, p=0.0008, n=9,605, and β=−0.11 mmol/l per G allele, 95% CI −0.15, −0.06, p<0.0001, n=9,517, respectively), but only in participants examined during the dark season ( p interaction =0.006 and 0.04, respectively). Repeated measures analyses including data collected 10 years after baseline (n=3,500) confirmed the results for the CRY1 locus ( p interaction =0.01). Conclusions/interpretation In summary, these observations suggest a biologically plausible season-dependent association between SNPs at CRY1, CRY2 and MTNR1B and glucose homeostasis.

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“…For instance, it has been reported that clock gene expression is impaired in individuals with metabolic syndrome, and, further, that impairments in transcript levels of PER3 in human leukocytes occur in diabetic subjects and gestational diabetic women [33,34]. Interestingly, mRNA of PER3 has been found to be inversely proportional to the glycated hemoglobin levels in T2DM patients [31,34]. Taken together, these findings suggest that impaired Per3 may influence glucose metabolism.…”

Section: Discussionmentioning

confidence: 88%

Per3 length polymorphism in patients with type 2 diabetes mellitus

Ramanujam

Marimuthu

Sooriyakumar

et al. 2013

Hormone Molecular Biology and Clinical Investigation

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Background: A number of observations support the involvement of circadian clock genes in the regulation of metabolic processes. One of these circadian genes, Per3, exhibits a variable number tandem repeat length polymorphism, consisting of two alleles, namely four and five repeat alleles, in its exon 18. The objective of this study was to examine the existence of Per3 variants in patients with type 2 diabetes mellitus (T2DM) as compared to a non T2DM control group. Methods: Intravenous blood samples were collected to obtain white blood cells from 302 T2DM patients and 330 non-diabetic, age-and sex-matched, individuals. Per3 genotyping was performed on DNA by polymerase chain reaction. Results: Frequency of five repeat allele was higher, and that of four repeat allele lower, in T2DM patients as compared to non-diabetic controls (χ 2 = 6.977, p = 0.0082) Conclusions:The results indicate an association of Per3 five repeat allele with T2DM occurrence and suggest that individuals with five repeat allele may be at a greater risk for T2DM as compared to those carrying the four repeat allele.

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Regulation of core clock genes in human islets

Cited by 86 publications

References 20 publications

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

Season-dependent associations of circadian rhythm-regulating loci (CRY1, CRY2 and MTNR1B) and glucose homeostasis: the GLACIER Study

Per3 length polymorphism in patients with type 2 diabetes mellitus

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