Enhanced effect of daytime restricted feeding on the circadian rhythm of streptozotocin-induced type 2 diabetic rats. Am J Physiol Endocrinol Metab 302: E1027-E1035, 2012. First published February 7, 2011 doi:10.1152/ajpendo.00651.2011There is increasing awareness of the link between impaired circadian clocks and multiple metabolic diseases. However, the impairment of the circadian clock by type 2 diabetes has not been fully elucidated. To understand whether and how the function of circadian clock is impaired under the diabetic condition, we examined not only the expression of circadian genes in the heart and pineal gland but also the behavioral rhythm of type 2 diabetic and control rats in both the nighttime restricted feeding (NRF) and daytime restricted feeding (DRF) conditions. In the NRF condition, the circadian expression of clock genes in the heart and pineal gland was conserved in the diabetic rats, being similar to that in the control rats. DRF shifted the circadian phases of peripheral clock genes more efficiently in the diabetic rats than those in the control rats. Moreover, the activity rhythm of rats in the diabetic group was completely shifted from the dark phase to the light phase after 5 days of DRF treatment, whereas the activity rhythm of rats in the control group was still under the control of the suprachiasmatic nucleus (SCN) after the same DRF treatment. Furthermore, the serum glucose rhythm of type 2 diabetic rats was also shifted and controlled by the external feeding schedule, ignoring the SCN rhythm. Therefore, DRF shows stronger effect on the reentrainment of circadian rhythm in the type 2 diabetic rats, suggesting that the circadian system in diabetes is unstable and more easily shifted by feeding stimuli. daytime restricted feeding; Clock genes; type 2 diabetes; pineal gland; heart LIFE ON EARTH IS GOVERNED by the 24-h light-dark (LD) environmental cycle. Numerous physiological processes such as sleep-wake cycle, behavior activity, cardiovascular function, etc., are coordinated to this 24-h cycle by an internal circadian timing system that is comprised of a hierarchy of circadian clocks (11,25,45). The mechanism underlying circadian clocks is composed of a set of interlocking transcription/translation feedback loops involving multiple clock genes [Clock, Bmal1, Per(s), Cry(s), Dec(s)] and their proteins (23, 28). These circadian clocks reside not only in the hypothalamic suprachiasmatic nucleus (SCN), which is recognized as the master clock, but also in almost all peripheral tissues, including liver, heart, and pineal gland (28,30,44).Malfunction of the biological clock is commonly present in our daily life. The modern lifestyle, including shift work, nocturnal activity, and late-night dietary, easily causes internal dyschronization. There is increasing awareness of the link between impaired circadian clocks and multiple metabolic diseases (26,33). It has been demonstrated that Clock mutant mice have an attenuated feeding rhythm and develop metabolic syndrome, including hyperglycemia...