Molecular circadian clock disruption in the leukocytes of individuals with type 2 diabetes and overweight, and its relationship with leukocyte–endothelial interactions
Authors' conclusion
Our study demonstrates alterations in the molecular clock system in leukocytes of individuals with type 2 diabetes, manifested in increased mRNA levels and decreased protein levels of the core clock machinery. These alterations correlated with the impaired metabolic and proinflammatory profile of the participants with type 2 diabetes. Our findings support a causal role for decreased CLOCK/BMAL1 activity in the increased level of leukocyte-endothelial interactions. Overall, our data suggest that alterations in core clock proteins accelerate the inflammatory process, which may ultimately precipitate the onset of CVD in patients with type 2 diabetes.
Study context
- Population
- Individuals with T2D and overweight vs healthy controls; peripheral blood leukocytes
- Participants
- 25 vs 28
- Exposure
- T2D vs healthy controls
- T2Dn = 25
- Healthy controlsn = 28reference
- Outcome
- Leukocyte molecular clock and leukocyte–endothelial interactions
Methodological detailsobservational
- Observational
Main finding
As reported in the abstract
- Increased BMAL1 and NR1D1 mRNA levels in T2D
- Decreased protein levels of circadian locomotor output cycles kaput (CLOCK), CRY1, p-BMAL1 and PER2 in T2D
- Clock protein alterations negatively associated with glucose, HbA1c, insulin, HOMA-IR and leukocyte counts
- Reduced leukocyte rolling velocity and enhanced rolling flux and adhesion in T2D vs healthy participants
- CLOCK inhibition with CLK8 mimicked the effects of T2D on leukocyte–endothelial interactions
Observational data: associations, not effects.
Original publication
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