Suprachiasmatic-controlled entry of glucose into the arcuate nucleus determines the rhythm in blood glycemia
The central biological clock, the suprachiasmatic nucleus (SCN), synchronizes behavior and physiological processes with the daily light/dark cycle to prepare the body optimally for the coming rest/activity period. According to the time of the day, the SCN establishes different set-points for some hormones and circulating metabolites. These set-points are adjusted to emergent conditions such as fasting, sickness, or stress (Mrosovsky, 1990). This subtle modulation of set-points is a result of a daily modulation of the sensitivity of various sensory structures (Buijs et al., 2019). For example, glucose levels and temperature oscillate with a higher amplitude when animals fast, with lower values at the beginning of the sleep phase (Zeitgeber Time (ZT) 2 in rodents), but reaching the same acrophase as an ad libitum animal just before the active period (ZT11 in rodents) (La Fleur et al., 1999; Liu et al., 2002). The arcuate nucleus (ARC) is essential for these processes detecting peripheral concentrations of hormones, metabolites, and glucose, thanks to its strategic position in the hypothalamus, next to the median eminence (ME), a circumventricular organ lacking of the blood-brain barrier with fenestrated capillaries (Ciofi, 2011; Rodríguez et al., 2010). The first-order neurons within the ARC are then allowed to rapidly detect peripheral signals (Faouzi et al., 2007; Fioramonti et al., 2007; Leon-Mercado et al., 2017; Parton et al., 2007; Schaeffer et al., 2013; Zhang and Van Den Pol, 2016). The control of corticosterone secretion exemplifies the importance of rapidly detecting blood-borne molecules by the ARC for regulatory processes. ARC neurons sense corticosterone providing a fast negative feedback to modify its secretion depending on the time of the day (Leon-Mercado et al., 2017). We hypothesized that circadian regulation of glucose levels follows a similar concept, whereby direct projections from the SCN to the ARC modify glucose sensing in the ARC throughout the day, thereby modulating peripheral glucose levels in a circadian manner. Based on that hypothesis, experiments were done in Wistar rats, and the raw data is available here. You can find pictures of permeability essays in the ARC, using Evans Blue, pictures from fluorescent immunohistochemistry showing differences in the morphology of the ME-ARC barrier, as well as in the content of GLUT-1. You can also find the raw data of the glycemia values in several conditions such as after receiving icv injections of GLUT-1 blocker, VP antagonist, and their respective control groups. Here you also have access to the statistic tests performed in each case. For details of each picture and a more elaborated description, please see the complete.