抄録
Myocardial infarction frequently occurs in the morning, a phenomena in part resulting from the down regulation of fibrinolytic activity. Plasminogen activator inhibitor-1 (PAI-1) is a key factor behind fibrinolytic activity, and its gene expression shows circadian change in the mouse heart and liver. Mouse Pai-1 transcription is seems to be controlled not only by clock genes but also by humoral factors such as insulin and triglyceride. Thus, we investigated daily clock genes and mPai-1 mRNA expression in the liver of db/db mice exhibiting high levels of glucose, insulin, and triglyceride. The rhythmic expression of mPer2 mRNA was severely dampened and the phase of mBmal1 oscillation was advanced in the db/db mouse liver, while mPai-1 mRNA was highly and constitutively expressed. Night-time restricted feeding led to a recovery from not only the dampened locomotor activity, but also from the dampened mPer2 and advanced mBmal1 mRNA rhythms. mPai-1 mRNA expression in db/db mice was reduced far below normal levels. High fat diet increased the mPai-1 gene expression in the liver of normal mice but not of clock mutant mice. In summary, we demonstrated that insulin-independent diabetes impaired the oscillation of the peripheral oscillator. Night-time restricted feeding led to a recovery from the dampened locomotor activity and altered oscillation of the peripheral clock and mPai-1 mRNA rhythm. In addition, circadian clock may affect mPai-1 gene expression through lipid metabolism. [Jpn J Physiol 55 Suppl:S25 (2005)]
