Conductor of the Astrocyte-Neuron Metabolic Orchestra

Abstract

Disorders such as diabetes mellitus, obesity, Parkinson’s, and Alzheimer’s diseases are characterized by central metabolic dysfunctions and pose an enormous economic burden to public health. Annually, several millions of new cases and deaths are reported worldwide, thus substantiating the need to search for new frontiers in combating the growing prevalence and mortality of these diseases. Over the past few years, scientific evidence has consistently shown that the functional sweet taste receptor, T1R2+T1R3 heterodimer, serves to direct (conduct) peripheral glucose metabolism. Recent data have revealed that this heterodimer can also act as a central glucosensor that conducts cerebral glucose metabolism. Emerging reports have confirmed the central role of this receptor as a driver of glucose metabolism in neurons and astrocytes. In this paper, “metabolic orchestra” is used to depict the organizational complexity of the plasma membrane receptor-network involved in coordinating glucose transport and metabolism in the astrocyte-neuron circuitry. In light of recent works, suggesting that the taste receptor is a crucial central glucosensor and master coordinator of glucose metabolism, here, the T1R2+T1R3 heterodimer is referred to as the metabolic conductor of the astrocyte-neuron circuitry, responsible for a highly coordinatedsignaling of glucose molecules and multi-directional cross-talk with other plasma membrane receptors. This concept represents a shift on the astrocyte-neuron metabolic machinery from the GLUT-2 mediated entry of glucose to a more coordinated one, involving multiple players at the plasma membrane. Research focusing on the treatments of brain disorders involving glucose metabolic dysfunctions is also discussed.