Suprachiasmatic Nucleus Neurons Are Glucose Sensitive

Abstract

The suprachiasmatic nucleus (SCN) in the hypothalamus serves as the pacemaker for mammalian circadian rhythms. In a hamster brain slice preparation, the authors were able to record spontaneous activity from SCN cells for up to 4 days in vitro and verify a self-sustained rhythm in firing. The phase of this rhythm was altered by the concentration of glucose in the bathing medium, with time of peak firing advanced for a 20 mM glucose condition and slightly delayed for a 5 mM glucose condition, relative to 10 mM. The advancing effect of 20 mM glucose and the delaying effect of 5 mM glucose were not maintained during a 2nd day in vitro after changing the bathing medium back to 10 mM glucose, thus indicating the effect was not a permanent phase shift of the underlying oscillation. In experiments recording from cell-attached membrane patches on acutely dissociated hamster SCN neurons, exchanging the bathing medium from high (20 mM) to zero glucose increased potassium (K+)-selective channel activity. With inside-out membrane patches, the authors revealed the presence of a glybenclamide-sensitive K+ channel (190 pS) and a larger conductance (260 pS) Ca(2+)-dependent K+ channel that were both reversibly inhibited by ATP at the cytoplasmic surface. Furthermore, 1 mM tetraethylammonium chloride was demonstrated to advance peak firing time in the brain slice in a similar manner to a high concentration of glucose (20 mM). The authors interpret the result to imply that SCNs are sensitive to glucose, most probably via ATP modulation of K+ channel activity in these neurons. Tonic modulation of K+ channel activity appears to alter output of the pacemaker but does not reset the phase.

Clock Genes and Behavioral Responses to Light Are Altered in a Mouse Model of Diabetic Retinopathy

“…The nature of this disturbance is unknown and can be related to alterations of cell metabolic activity of the retina and/or the SCN itself. Previous studies have shown that changes in brain glucose metabolism attenuate the entraining effects of light on the circadian pacemaker [57] and advance the phase of the rhythmic firing rate of the SCN [58].…”

Circadian phenotyping of obese and diabetic db/db mice

“…By contrast, streptozotocin-induced hyperglycemia in mice increase the shifting effect of light during early night [20]. Furthermore, glucose has been shown to alter the circadian firing rate of SCN slice in vitro [33]. Glucose uptake of neurons being independent of insulin [34], the increase of glucose availability in db/db mice may affect the metabolic activity of SCN cells.…”

Metabolic and reward feeding synchronises the rhythmic brain

“…leptin, insulin or ghrelin) and metabolites (e.g. glucose, free fatty acids or ketone bodies) may act on SCN cells (Hall et al 1997;Prosser and Bergeron 2003;Yannielli et al 2007;Yi et al 2008). Otherwise, the altered cellular metabolic state might affect the molecular clockwork (Rutter et al 2002).…”