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Neuronal Glucosensing

What Do We Know After 50 Years?

¹ Neurology Service, Department of Veterans Affairs New Jersey Health Care System, East Orange, New Jersey
² Department of Neurology and Neurosciences, New Jersey Medical School, University of Medicine and Dentistry, Newark, New Jersey
³ Department of Pharmacology and Physiology, New Jersey Medical School, University of Medicine and Dentistry, Newark, New Jersey
⁴ Metabolism/Endocrinology Service, VA Puget Sound Health Care System, Seattle, Washington

Glucosensing neurons are specialized cells that use glucose as a signaling molecule to alter their action potential frequency in response to variations in ambient glucose levels. Glucokinase (GK) appears to be the primary regulator of most neuronal glucosensing, but other regulators almost certainly exist. Glucose-excited neurons increase their activity when glucose levels rise, and most use GK and an ATP-sensitive K⁺ channel as the ultimate effector of glucose-induced signaling. Glucose-inhibited (GI) neurons increase their activity at low glucose levels. Although many use GK, it is unclear what the final pathway of GI neuronal glucosensing is. Glucosensing neurons are located in brain sites and respond to and integrate a variety of hormonal, metabolic, transmitter, and peptide signals involved in the regulation of energy homeostasis and other biological functions. Although it is still uncertain whether daily fluctuations in blood glucose play a specific regulatory role in these physiological functions, it is clear that large decreases in glucose availability stimulate food intake and counterregulatory responses that restore glucose levels to sustain cerebral function. Finally, glucosensing is altered in obesity and after recurrent bouts of hypoglycemia, and this altered sensing may contribute to the adverse outcomes of these conditions. Thus, although much is known, much remains to be learned about the physiological function of brain glucosensing neurons.

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