Browsing by Subject "Glut-1"

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GLUT-1 content and interaction with stomatin in red blood cells from species without vitamin C biosynthesis and their relevance for diabetes mellitus type 1
(2016) Frey, Tabea Caroline; Biesalski, Hans-Konrad
Ascorbic acid is commonly known as vitamin C. By definition, vitamins, with the exception of vitamin D, are substances which can not be synthesized, but are essential for the organism. In this light, vitamin C is special. It is hypothesized that millions of years ago some species, like primates, Guinea pigs and fruit bats, lost the ability to synthesize ascorbate from glucose due to an inactivation of an enzyme called L-gulono-g-lactone oxidase. Since then, these species have been dependent on dietary intake of this micronutrient. Ascorbate is not only the most efficient watersoluble antioxidant, but also an important cofactor in neurotransmitter or collagen biosynthesis. An inadequate intake of this vitamin leads to scurvy. In 2008, a French researcher documented that all species that lost the ability to synthesize ascorbic acid express a different facilitative glucose transporter isoform(GLUT) in their erythrocytes. The expressed GLUT-1 transports not only glucose but also dehydroascorbate which is the oxidized form of vitamin C. Was that different GLUT expression the keystone event for the evolutionary success of these species? To examine the questions regarding the evolutionary benefit of this transporter expression, the kinetics of ascorbate and dehydroascorbate transport into erythrocytes from four different species were evaluated. Further, recycling and disposal of the transported vitamin as well as a possible accumulation were observed. The results demonstrate that there are three different transport types of dehydroascorbate. One which does not transport the vitamin at all, one whose transport of dehydroascorbate competes with glucose and one which absorbs dehydroascorbate completely independent of the extracellular glucose concentration. After absorption, vitamin C is not recycled and is not disposed back into the extracellular fluid. Additionally, it is not stored in the cell until the erythrocyte undergoes apoptosis. The evolutionary benefit is found in an electron transfer across the erythrocyte membrane from intracellular ascorbate to the extracellular, oxidized form of vitamin C. In an energetic light, this recycling of extracellular vitamin C is more efficient than the de novo synthesis of the micronutrient. Therefore, the erythrocyte acts not as a reservoir for vitamin C storage, but as a reservoir for electron storage to prevent degradation and loss of dehydroascorbate in times of high oxidative stress. This electron reservoir becomes more important in diseases with high levels of oxidative stress. A metabolic disorder, which is frequently described to be accompanied by high levels of oxidative stress and lowered vitamin C levels in plasma and cells, is Diabetes mellitus. The decreased plasma concentrations do not result from a smaller dietary intake. Probably, the uptake of dehydroascorbate into erythrocytes, and, therefore, the extracellular ascorbate recycling is disordered. Investigations of the distribution of GLUT-1 in different erythrocyte membrane subdomains showed that the regulation of this transporter is altered in subjects with diabetes mellitus type 1 compared to healthy controls. In vitro, no differences in dehydroascorbate transport rate could be observed, but significantly decreased intra-erythrocyte vitamin C concentrations were detected in vivo. In conclusion, the altered regulation of GLUT-1 in the erythrocyte membrane in the case of diabetes can affect vitamin C recycling in plasma. A decreased ascorbate pool in the cells leads to a decreased recycling capacity, and, therefore, to a lower antioxidant defense outside the cell. Due to that knowledge, the recommended dietary intake of vitamin C in the case of diabetes mellitus must be reconsidered to prevent further complications.