Effect Of Circadian Clock Regulation Of The Diabetic Biorhythm

There are increasing awareness of the links between impaired circadian clocks and multiple metabolic diseases. However, the impairment of the circadian clock induced by type2diabetes has not been fully elucidated. To understand whether and how the function of circadian clock is impaired under the diabetic condition, we investigated both the individual and combined effects of light and food cure on the expression of circadian genes in the peripheral organs and behavioral rhythm in the type2diabetic and normal rats. In addition, we also examined the glucose metabolism and PAI-1variation in normal and diabetic rats under different conditions.Results obtained here indicated that circadian gene expression was generally conserved in heart and pineal gland in diabetic rats under nighttime restricted feeding (NRF) condition, with only a few phase shifted clock genes in the liver. However, the amplitude of examined clock genes was altered in peripheral tissues of diabetic rats. After reversing the feeding schedule, most of the clock genes in the heart of diabetic rats finished their re-entrainment within5days, while only Cryl in normal group finished the circadian resetting at the same time. On the other hand, the phases of most pineal clock genes were shifted in the diabetic rats, which were almost not affected in the normal rats under NRF. After reversing the LD cycle, part of peripheral clock genes in the liver of diabetic rats had a faster resetting process than those in the normal rats. After reversing both feeding schedule and LD cycle, the examined clock genes of normal rats finished their re-entrainment within3-5days, while those in the diabetic rats took a longer time to adapt this jet lag. Moreover, the activity rhythm of diabetic rats was unstable and much easier to shift by the feeding schedule, even uncoupling from the SCN clock. However, the resetting speed of the diabetic rats under jet lag condition was much slower than that of the normal rats. Therefore, the diabetic rats are more sensitive to the individule food stimuli, but they are unable to adapt to the jet lag as quickly as normal rats do.In addition, the expression level of plasminogen activator inhibitor-1(PAI-1) in diabetic rats was much higher than normal rats. When the rats were kept under the reversed feeding or lighting schedule, PAI-1showed a significant change in both groups, suggesting the cardiovascular function was significantly affected. Therefore, it is especially important for the diabetic patients to keep a good living habit to minimize their circadian disorders under the accelerating modern life.