Fate of glucose in the brain: effects of some xenobiotics

Abstract

Glucose is a common nutrient for many cells in the body. However, in the brain, some aspects of its metabolism remain unclear. To better understand the role of glucose in the brain, we propose in the present study to follow its molecule from the digestive tract to its metabolites in the neural cells. Moreover, we show the influence of some xenobiotics on the fate of the glucose, and on the expression of some related genes in the brain. After food intake, the glucose molecule reaches the body cells using plasma filtration, except in the brain. In the latter, because of the blood brain barrier, glucose, which is largely hydrophilic, uses glucose transporters to reach the neural cells. Then, it follows four main pathways. Two of them are catabolic pathways and comprise glycolysis on the one hand and the formation of ribose-5-phosphate pathway on the other. Two other ways are anabolic pathways - glycogen synthesis and gluconeogenesis. Xenobiotics such as the stimulant amphetamine decrease the glycogen content in the brain, using the adrenoreceptor and cAMP signalling, as does norepinephrine. Recent investigations show that this decrease is transient and is followed by a large increase in the glycogen level through the over expression of the mRNA of the regulatory subunit of the protein phosphatase 1, the protein targeting to glycogen. Another xenobiotic, methionine sulfoximine, increases the glycogen content and enhances the mRNA expressions of some enzymes related to the glucose pathways in the brain. Gluconeogenesis perhaps contributes to the methionine sulfoximine effect. Some points of the fate of glucose are still unclear: the low level of free glucose in the brain parenchyma, the fate of the metabolite lactate, and the contribution of gluconeogenesis to glycogen accumulation.