Daily profile of glut1 and glut4 expression in tissues inside and outside the blood-brain barrier in control and streptozotocin-treated rats.

Glucose is molecule usually studied in relation to metabolism. Except for this traditional view, it is known that under certain conditions glucose can serve as a signal molecule for the circadian system. The circadian system is entrained by relevant synchronizing cues that can be tissue-dependent. Central oscillator is synchronized mainly by light-dark cycle, while peripheral oscillators can be entrained by food intake. Glucose transport in the organism is controlled by insulin dependent and independent mechanism. Therefore, we employed streptozotocin-induced diabetes to elucidate the influence of metabolic changes on glucose transporter (glut1, glut4) 24-h expression profile in peripheral oscillators in tissues, inside (frontal cortex, cerebellum) and outside (heart) the blood-brain barrier. Diabetes was induced by streptozotocin injection. Seventeen days later, sampling was performed during a 24-h cycle. Gene expression was measured using real-time PCR. We observed down-regulation of glut1 and glut4 expression in the heart of diabetic rats. The expression of glut1 and glut4 in brain areas was not down-regulated, however, we observed trend to phase advance in glut1 expression in the cerebellum. These results may indicate higher glucose levels in diabetic brain, which might influence regulation of clock gene expression in different manner in brain compared to periphery.

Effect of streptozotocin-induced diabetes on clock gene expression in tissues inside and outside the blood-brain barrier in rat.

The circadian system allows organisms to remain synchronized with rhythmic environmental changes with a 24-h period. The molecular mechanism of circadian oscillations is based on the rhythmic expression of clock genes organized in feedback loops. Alterations in the circadian system contribute to the development of several pathological conditions including diabetes, but the exact mechanisms responsible for such alterations are not known. Therefore, we employed streptozotocin-induced diabetes to elucidate the influence of metabolic changes on clock gene (clock, npas2, per2) expression in peripheral oscillators in tissues inside (frontal cortex, cerebellum) and outside (heart, kidney) the blood-brain barrier. Diabetes was induced by streptozotocin injection. Seventeen days later, sampling was performed during a 24-h cycle. Gene expression was measured using real-time PCR. We observed a phase advance in rhythmic clock gene expression in the heart and kidney of diabetic rats. The study also focused on the possible role of npas2 in locomotor activity regulation in diabetic animals. The most pronounced changes were observed in the frontal cortex, which displayed up-regulation of npas2 expression. A change in locomotor activity was observed in diabetic rats during the dark phase of the 24-h cycle. We suggest that the altered function of the frontal cortex induced by diabetes might contribute to the modified behavior of diabetic rats.