Suprachiasmatic nucleus-mediated glucose entry into the arcuate nucleus determines the daily rhythm in blood glycemia.

Glycemia is maintained within very narrow boundaries with less than 5% variation at a given time of the day. However, over the circadian cycle, glycemia changes with almost 50% difference. How the suprachiasmatic nucleus, the biological clock, maintains these day-night variations with such tiny disparities remains obscure. We show that via vasopressin release at the beginning of the sleep phase, the suprachiasmatic nucleus increases the glucose transporter GLUT1 in tanycytes. Hereby GLUT1 promotes glucose entrance into the arcuate nucleus, thereby lowering peripheral glycemia. Conversely, blocking vasopressin activity or the GLUT1 transporter at the daily trough of glycemia increases circulating glucose levels usually seen at the peak of the rhythm. Thus, biological clock-controlled mechanisms promoting glucose entry into the arcuate nucleus explain why peripheral blood glucose is low before sleep onset.

The suprachiasmatic nucleus; a responsive clock regulating homeostasis by daily changing the setpoints of physiological parameters.

The suprachiasmatic nucleus (SCN) is responsible for determining circadian variations in physiological setpoints. The SCN achieves such control through projections to different target structures within and outside the hypothalamus. Thus the SCN prepares the physiology of the body every 24 h via hormones and autonomic nervous system (ANS), to coming changes in behavior. Resulting rhythms in hormones and ANS activity transmit a precise message to selective organs, adapting their sensitivity to coming hormones, metabolites or other essentials. Thus the SCN as autonomous clock gives rhythm to physiological processes. However when the body is challenged by infections, low or high temperature, food shortage or excess: physiological setpoints need to be changed. For example, under fasting conditions, setpoints for body temperature and glucose levels are lowered at the beginning of the sleep (inactive) phase. However, starting the active phase, a normal increase in glucose and temperature levels take place to support activities associated with the acquisition of food. Thus, the SCN adjusts physiological setpoints in agreement with time of the day and according to challenges faced by the body. The SCN is enabled to do this by receiving extensive input from brain areas involved in sensing the condition of the body. Therefore, when the body receives stimuli contradicting normal physiology, such as eating or activity during the inactive period, this information reaches the SCN, adapting its output to correct this disbalance. As consequence frequent violations of the SCN message, such as by shift work or night eating, will result in development of disease.