Cellular circadian period length inversely correlates with HbA<sub>1c</sub> levels in individuals with type 2 diabetes.
Details
Serval ID
serval:BIB_5E930758B719
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cellular circadian period length inversely correlates with HbA<sub>1c</sub> levels in individuals with type 2 diabetes.
Journal
Diabetologia
ISSN
1432-0428 (Electronic)
ISSN-L
0012-186X
Publication state
Published
Issued date
08/2019
Peer-reviewed
Oui
Volume
62
Number
8
Pages
1453-1462
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
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.
Keywords
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
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Create date
14/06/2019 17:12
Last modification date
27/04/2020 6:20
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