Circadian entry of glucose into the arcuate nucleus determines the rhythm in blood glycemia

Abstract

Circulating glucose 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 small variations 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, adjusting circulating glucose to its lowest level. Conversely, blocking vasopressin activity or the GLUT1 transporter at the daily trough of glycemia, increases circulating glucose to levels usually seen at the peak of the rhythm. Thus, biological clock-controlled mechanisms promoting glucose entry into the arcuate nucleus before sleep sets the circadian low-glucose levels.Fasting promotes an increase in arcuate GLUT1 and glucose, followed by lowering circulating glucose levels, supporting the essential role of this mechanism for controlling circulating glucose levels.