📝 ATP-Sensitive Potassium Channel-Mediated Lactate Effect On Orexin Neurons: Implications For Brain Energetics During Arousal

The brain, although comprising only 2% of body weight, is responsible for 25% of total body glucose utilization, necessitating a continuous supply from the periphery (Magistretti et al., 1995). This is thought to be ensured by the glucose homeostatic mechanism involving “glucosensors” that exist in the hypothalamus and brainstem (Levin et al., 2004; Marty et al., 2007). Glucosensing neurons are excited [glucose excited (GE)] or inhibited [glucose inhibited (GI)] by extracellular glucose and induce appropriate counterregulatory responses to restore glucose homeostasis (Levin, 2001). Glucosensing in certain GE and GI neurons depends on glucokinase, a critical enzyme that catalyzes glycolysis (Lynch et al., 2000; Dunn-Meynell et al., 2002; Kang et al., 2004; Balfour et al., 2006), suggesting that glucose metabolism is directly involved in their electrophysiological response to glucose.