Brain glucose sensing: a subtle mechanism

Brain nutrient sensing allows a fine regulation of different physiological functions, such as food intake and blood glucose, related to energy homeostasis. Glucose sensing is the most studied function and a parallel has been made between the cellular mechanisms involved in pancreatic beta cells and neurons.

Two types of glucosensing neurons have been characterized--those for which the activity is proportional to changes in glucose concentration and those for which the activity is inversely proportional to these changes. A new level of complexity has recently been demonstrated, as the response and the mechanism appear to vary in function according to the level of the glucose change. For some of the responses, the detection is probably not at the level of the neuron itself, but astrocytes also appear to be involved, indicating a coupling between the two types of cells. Finally, numerous data have demonstrated the modulation of glucose sensing by other nutrients, in particular fatty acids, hormones (insulin, leptin and ghrelin) and peptides (neuropeptide Y). This implies a common pathway in which AMPkinase may play a crucial role.

Recent observations in brain nutrient sensing indicate subtle mechanisms, with different cellular and molecular mechanisms involved. This fact would explain the discrepancies reported in the expression of different proteins (glucose transporters, hexokinases, channels). Astrocytes may be involved in one type of response, thus adding a new level of complexity.