Cellular circadian period length inversely correlates with HbA<sub>1c</sub> levels in individuals with type 2 diabetes.

Détails

ID Serval
serval:BIB_5E930758B719
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cellular circadian period length inversely correlates with HbA<sub>1c</sub> levels in individuals with type 2 diabetes.
Périodique
Diabetologia
Auteur(s)
Sinturel F., Makhlouf A.M., Meyer P., Tran C., Pataky Z., Golay A., Rey G., Howald C., Dermitzakis E.T., Pichard C., Philippe J., Brown S.A., Dibner C.
ISSN
1432-0428 (Electronic)
ISSN-L
0012-186X
Statut éditorial
Publié
Date de publication
08/2019
Peer-reviewed
Oui
Volume
62
Numéro
8
Pages
1453-1462
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The circadian system plays an essential role in regulating the timing of human metabolism. Indeed, circadian misalignment is strongly associated with high rates of metabolic disorders. The properties of the circadian oscillator can be measured in cells cultured in vitro and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo. We aimed to discover whether molecular properties of the circadian oscillator are altered as a result of type 2 diabetes.
We assessed molecular clock properties in dermal fibroblasts established from skin biopsies taken from nine obese and eight non-obese individuals with type 2 diabetes and 11 non-diabetic control individuals. Following in vitro synchronisation, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters.
We observed a significant inverse correlation (ρ = -0.592; p < 0.05) between HbA <sub>1c</sub> values and circadian period length within cells from the type 2 diabetes group. RNA sequencing analysis conducted on samples from this group revealed that ICAM1, encoding the endothelial adhesion protein, was differentially expressed in fibroblasts from individuals with poorly controlled vs well-controlled type 2 diabetes and its levels correlated with cellular period length. Consistent with this circadian link, the ICAM1 gene also displayed rhythmic binding of the circadian locomotor output cycles kaput (CLOCK) protein that correlated with gene expression.
We provide for the first time a potential molecular link between glycaemic control in individuals with type 2 diabetes and circadian clock machinery. This paves the way for further mechanistic understanding of circadian oscillator changes upon type 2 diabetes development in humans.
RNA sequencing data and clinical phenotypic data have been deposited at the European Genome-phenome Archive (EGA), which is hosted by the European Bioinformatics Institute (EBI) and the Centre for Genomic Regulation (CRG), ega-box-1210, under accession no. EGAS00001003622.
Mots-clé
Adult, Aged, Biopsy, Blood Glucose/metabolism, CLOCK Proteins/metabolism, Circadian Clocks/genetics, Circadian Rhythm, Diabetes Mellitus, Type 2/blood, Female, Fibroblasts/metabolism, Glycated Hemoglobin A/analysis, Humans, Intercellular Adhesion Molecule-1/metabolism, Lentivirus/metabolism, Male, Middle Aged, Phenotype, Sequence Analysis, RNA, Skin/metabolism, Circadian bioluminescence recording, Circadian clock, HbA1c, ICAM1, Type 2 diabetes
Pubmed
Web of science
Création de la notice
14/06/2019 17:12
Dernière modification de la notice
27/04/2020 6:20
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