Db/db
mouse, which lacks functional leptin receptor, is an extensively used model of obesity and type 2 diabetes. We and others have demonstrated that
db/db
mouse has disruptions in circadian rhythms of behavior, physiology and some clock genes. However, systemic investigations of the alterations in clock gene oscillations in multiple systems with high time resolution in this model are impeded by the impractical demand for large number of animals. To overcome this limitation, we cross bred the
db/db
mouse with
mPer2
Luc
mouse in which the clock gene
Period2
is fused with a luciferase reporter thus allow real-time monitoring of the clock gene
Per2
oscillations. The generated
db/db-mPer2
Luc
mice had the typical diabetic mellitus including obesity, hyperglycemia, hyperinsulinemia, glucose intolerance and insulin resistance. In addition, the
db/db-mPer2
Luc
mice also exhibited disruptions in circadian rhythms in behavior (locomotor activity), physiology (blood pressure) and metabolism (respiratory exchange ratio and energy expenditure). Using the LumiCycle system, we monitored in real-time of the
Per2
oscillations in both the SCN central clock and multiple peripheral tissues
ex vivo
. The results showed no difference in the phase of the central SCN
Per2
oscillation. However, the peripheral tissues that related to metabolism, such as liver and white adipose clocks, displayed 3.28±0.86 and 4.64±1.06 hours of phase advance respectively. Aorta, mesentery artery and kidney, organs play important role in blood pressure homeostasis, showed 0.99±0.37, and 2.12±0.4, and 2.21±0.5 hours phase advance respectively. Interestingly, no difference was observed in the lung and adrenal gland. We then investigated the
Per2
oscillation
in vivo
by using the IVIS imaging system. Consistent with the
ex vivo
results, the liver
Per2
oscillation were phase advanced in vivo. Our findings demonstrated that clock gene
Per2
oscillations were disrupted in multiple peripheral tissues but not in central SCN. Moreover, the extent of phase advance in peripheral tissue varies largely. Our results suggest dyssynchrony of the clock oscillations among various peripheral systems likely contribute to the multiple disruptions in physiology and metabolism in diabetic
db/db
mice.