ABSTRACT
ObjectiveTo investigate the impacts of circadian misalignment on glucose uptake of skeletal muscle and metabolism in rats. MethodsA total of 36 male Wistar rats were divided into circadian alignment (CA, normal light-dark cycles, n = 18) and circadian misalignment (CM, shifted light-dark cycles, n = 18) groups. ClockLab behavior analysis was performed for 18 days (61 to 78 days after modeling). Intraperitoneal injection glucose tolerance test and physiologic measures were performed 85 days after modeling. They were euthanized 91 to 92 days after modeling, at 8:00, 12:00, 16:00, 20:00, 24:00 and 4:00 next day. Gastrocnemius tissue was collected and measured for Bmal1, Clock, Per2, Tbc1d1, Glut4 and Pgc1α by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR). ResultsThe circadian cycle increased (t = -6.557, P < 0.001), the amplitude decreased (t = 2.326, P = 0.030) and the area under curve (AUC) of the blood glucose of intraperitoneal glucose tolerance test decreased (t = -2.622, P = 0.016) in CM group. In gastrocnemius, there was difference in the expression of the Bmal1 (F = 6.691, P < 0.001), Clock (F = 4.188, P = 0.007), Per2 (F = 10.893, P < 0.001), Tbc1d1 (F = 3.411, P = 0.018), Glut4 (F = 5.439, P = 0.002) and Pgc1α (F = 15.376, P < 0.001) across different time; meanwhile, there was difference in the expression of Bmal1 (F = 5.020, P = 0.035), Per2 (F = 8.996, P = 0.006), Tbc1d1 (F = 51.111, P < 0.001) and Pgc1α (F = 10.177, P = 0.004) between groups, and the total Tbc1d1 expression decreased in CM group (t = 4.349, P < 0.001). ConclusionCM induced by shifted light-dark cycles may lead to glucose tolerance impairment in rats, which may be related to the decreased expression of Tbc1d1 and the changes of transcription rhythm of Bmal1, Per2 and Pgc1α in gastrocnemius.