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Circadian Clock Properties of T2D Patients

ABSTRACT: The circadian system plays an essential role in regulating timing of body metabolism in humans. Indeed, circadian misalignments are strongly associated with high rates of metabolic disorders. Molecular makeup of the circadian oscillator can be deciphered in cells cultured in vitro, and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo. We aimed at assessing molecular clock properties in dermal fibroblasts established from the skin biopsies of seventeen Type 2 diabetic obese and non-obese patients and eleven healthy controls. Following in vitro synchronization, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters. We observed a strong inverse correlation between HbA1c values and circadian period length within cells from the Type 2 diabetic group. RNA sequencing analysis conducted in this group samples revealed that ICAM1 encoding for the endothelial adhesion protein was differentially expressed between Type 2 diabetic compensated and non-compensated fibroblasts, and correlated with the period length. Furthermore, ICAM1 expression is driven by rhythmic CLOCK binding. We provide for the first time a potential molecular link between severity of Type 2 diabetes and circadian clock machinery, which paves a way for further mechanistic understanding of circadian oscillator changes upon Type 2 diabetes in humans.

PROVIDER: EGAS00001003622 | EGA |

REPOSITORIES: EGA

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Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients [transcriptome analysis]

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cb7eb312-831c-415e-b971-d86dcd643ecf - samples

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