Suprachiasmatic nucleus promotes hyperglycemia induced by sleep delay

Abstract

Short sleep is linked to disturbances in glucose metabolism and may induce a prediabetic condition. The biological clock in the suprachiasmatic nucleus (SCN) regulates the glucose rhythm in the circulation and the sleep-wake cycle. SCN vasopressin neurons (SCN^VP) control daily glycemia by regulating the entrance of glucose into the arcuate nucleus (ARC). Thus, we hypothesized that sleep delay may influence SCN neuronal activity. We, therefore, investigated the role of SCN^VP when sleep is disrupted by forced locomotor activity. After 2 h of sleep delay, rats exhibited decreased SCN^VP neuronal activity, a decrease in the glucose transporter GLUT1 expression in tanycytes lining the third ventricle, lowered glucose entrance into the ARC, and developed hyperglycemia. The association between reduced SCN^VP neuronal activity and hyperglycemia in sleep-delayed rats was evidenced by injecting intracerebroventricular vasopressin; this increased GLUT1 immunoreactivity in tanycytes, thus promoting normoglycemia. Following sleep recovery, glucose levels decreased, whereas SCN^VP neuronal activity increased. These results imply that sleep-delay-induced changes in SCN^VP activity lead to glycemic impairment, inferring that disruption of biological clock function might represent a critical step in developing type 2 diabetes.

Keywords: GLUT1; arcuate nucleus; insulin sensitivity; locomotor activity; sleep deprivation; tanycytes; type 2 diabetes; vasopressin.