Clock Gene Expression in the Liver and Adipose Tissues of Non-Obese Type 2 Diabetic Goto-Kakizaki Rats

Ando, Hitoshi; Ushijima, Kazuo; Yanagihara, Hayato; Hayashi, Yohei; Takamura, Toshinari; Kaneko, Shuichi; Fujimura, Akio

doi:10.1080/10641960902822450

Cited by 23 publications

(18 citation statements)

References 24 publications

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“…The C/ebpα gene has divergent roles and functions, especially in glucose metabolism [10], [35], [36]. These findings also suggest close links between the circadian clock-controlled gene, C/ebpα and metabolic activity.…”

Section: Discussionmentioning

confidence: 97%

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The Circadian Binding of CLOCK Protein to the Promoter of C/ebpα Gene in Mouse Cells

et al. 2013

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C/EBPα plays important roles in metabolism as well as in the maintenance of energy homeostasis. Here we describe loss of the circadian oscillation of C/ebpα expression in liver of Clock mutant mice. Reporter assays indicate Clock and Bmal significantly induced C/ebpα gene expression whereas Cry suppressed. Real time reporter assays showed that two mutated E-boxes disrupted C/ebpα promoter dependent-oscillation. Chromatin immunoprecipitation suggests Clock can bind to two E-boxes in the C/ebpα promoter with a circadian manner in vivo. Thus, C/ebpα gene transcription is under circadian control of a core clock component, Clock. The data suggests that circadian disturbances may affect metabolic abnormalities through the C/ebpα pathway in liver.

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Section: Discussionmentioning

confidence: 97%

“…Recent studies have revealed an association between the circadian clock disruption and metabolic syndrome [28], [33]–[35]. The C/ebpα gene has divergent roles and functions, especially in glucose metabolism [10], [35], [36].…”

Section: Discussionmentioning

confidence: 99%

The Circadian Binding of CLOCK Protein to the Promoter of C/ebpα Gene in Mouse Cells

et al. 2013

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“…Recent studies have revealed an association between the circadian clock and metabolic diseases such as metabolic syndrome and diabetes (10,45). The rates of glycogen synthesis and the glycogen contents in the livers of patients with diabetes are significantly decreased (46).…”

Section: Discussionmentioning

confidence: 99%

CLOCK Regulates Circadian Rhythms of Hepatic Glycogen Synthesis through Transcriptional Activation of Gys2

Doi

Oishi

Ishida

2010

Journal of Biological Chemistry

125

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Hepatic glycogen content is important for glucose homeostasis and exhibits robust circadian rhythms that peak at the end of the active phase in mammals. The activities of the rate-limiting enzymes for glycogenesis and glycogenolysis also show circadian rhythms, and the balance between them forms the circadian rhythm of the hepatic glycogen content. However, no direct evidence has yet implicated the circadian clock in the regulation of glycogen metabolism at the molecular level. We show here that a Clock gene mutation damps the circadian rhythm of the hepatic glycogen content, as well as the circadian mRNA and protein expression of Gys2 (glycogen synthase 2), which is the rate-limiting enzyme of glycogenesis in the liver. Transient reporter assays revealed that CLOCK drives the transcriptional activation of Gys2 via two tandemly located E-boxes. Chromatin immunoprecipitation assays of liver tissues revealed that CLOCK binds to these E-box elements in vivo, and real time reporter assays showed that these elements are sufficient for circadian Gys2 expression in vitro. Thus, CLOCK regulates the circadian rhythms of hepatic glycogen synthesis through transcriptional activation of Gys2.

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“…Furthermore, STZ-mice develop a deficiency in their ability to re-entrain the circadian rhythm when subjected to a phase advance of the 12L/12D cycle [21]. Bio-Breeding Zucker diabetic rat (BBZDR/Wor) and Goto-Kakizaki rat type 2 diabetes (T2D) models also show impairment of the molecular clock, suggesting that the disruption of the circadian clock is a common phenomenon in both T1D and T2D [15,22].…”

Section: Introductionmentioning

confidence: 99%

Diurnal Rhythmicity of Autophagy Is Impaired in the Diabetic Retina

Mitter

Yan

et al. 2020

Cells

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Retinal homeostasis is under both diurnal and circadian regulation. We sought to investigate the diurnal expression of autophagy proteins in normal rodent retina and to determine if this is impaired in diabetic retinopathy. C57BL/6J mice and Bio-Breeding Zucker (BBZ) rats were maintained under a 12h/12h light/dark cycle and eyes, enucleated over a 24 h period. Eyes were also collected from diabetic mice with two or nine-months duration of type 1 diabetes (T1D) and Bio-Breeding Zucker diabetic rat (BBZDR/wor rats with 4-months duration of type 2 diabetes (T2D). Immunohistochemistry was performed for the autophagy proteins Atg7, Atg9, LC3 and Beclin1. These autophagy proteins (Atgs) were abundantly expressed in neural retina and endothelial cells in both mice and rats. A differential staining pattern was observed across the retinas which demonstrated a distinctive diurnal rhythmicity. All Atgs showed localization to retinal blood vessels with Atg7 being the most highly expressed. Analysis of the immunostaining demonstrated distinctive diurnal rhythmicity, of which Atg9 and LC3 shared a biphasic expression cycle with the highest level at 8:15 am and 8:15 pm. In contrast, Beclin1 revealed a 24-h cycle with the highest level observed at midnight. Atg7 was also on a 24-h cycle with peak expression at 8:15 am, coinciding with the first peak expression of Atg9 and LC3. In diabetic animals, there was a dramatic reduction in all four Atgs and the distinctive diurnal rhythmicity of these autophagy proteins was significantly impaired and phase shifted in both T1D and T2D animals. Restoration of diurnal rhythmicity and facilitation of autophagy protein expression may provide new treatment strategies for diabetic retinopathy.

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Clock Gene Expression in the Liver and Adipose Tissues of Non-Obese Type 2 Diabetic Goto-Kakizaki Rats

Cited by 23 publications

References 24 publications

The Circadian Binding of CLOCK Protein to the Promoter of C/ebpα Gene in Mouse Cells

The Circadian Binding of CLOCK Protein to the Promoter of C/ebpα Gene in Mouse Cells

CLOCK Regulates Circadian Rhythms of Hepatic Glycogen Synthesis through Transcriptional Activation of Gys2

Diurnal Rhythmicity of Autophagy Is Impaired in the Diabetic Retina

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