Reports

The circadian clock is an intrinsic time-keeping mechanism that controls the daily rhythms of numerous physiological processes, such as sleep/wake behavior, body temperature, hormone secretion, and metabo-lism (1–3). Circadian rhythms are generated in a cell-autonomous man-ner through transcriptional regulatory networks of clock genes. In the core feedback loop, the transcription factors CLOCK and BMAL1 acti-vate expression of Period (Per1 and Per2) and Cryptochrome (Cry1 and Cry2) genes. After translation and nuclear localization, PER and CRY proteins inhibit CLOCK-BMAL1 function, resulting in rhythmic gene expression (1–3). Rate-limiting steps in many physiological pathways, including hepatic processes, are under the control of the circadian clock (1–3). The gluconeogenic genes phosphoenol pyruvate carboxykinase (Pck1) and glucose 6-phosphatase (G6pc) are controlled by CRY and the nuclear receptor REV-ERB (4–6). Perturbations to clock function by genetic mutations or environmen