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Placental transport and metabolism
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Glucose transport is facilitated by a family of isoforms with the prefix GLUT. In human placenta, six GLUT isoforms have been identified at the mRNA level (35,36). The major placental GLUTs are GLUT1 and GLUT3 (37–39), whose abundance and activity differ in response to a variety of environmental factors, including diabetes, maternal nutritional status, hypoxia, and reduced uterine blood flow (28). These GLUTs have different kinetic activity and are differentially expressed within the placental membranes. GLUT3 occurs in the MVM at the maternal–fetal interface and is presumed to be responsible for the rate of glucose delivery to the fetus. GLUT1 tends to be located in the plasma BM and may modulate placental glucose consumption as well as being the rate-limiting step in transplacental glucose transport (39,40).
Vitamin C Alimentation via SLC Solute Carriers
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Damian Nydegger, Gergely Gyimesi, Matthias A. Hediger
The mechanisms of vitamin C delivery into the brain have already been discussed. Neurons require relatively high amounts of vitamin C, since they have a high rate of oxidative metabolism compared to other cells, leading to the oxidation of ascorbic acid to DHA. The mechanisms of ascorbic acid recycling are presented in Figure 3.3. DHA leaves the neurons, avoiding toxic effects of DHA accumulation. DHA efflux is facilitated via the GLUT3 transporter. Via the GLUT1 transporter, DHA is then imported into astrocytes. Astrocytes do not express SVCT2, but they take up DHA via GLUT1, which is then converted back into ascorbic acid [2,18]. Mechanisms for conversion into vitamin C involve glutathione and reducing enzymes. Indeed, the glutathione level of astrocytes is four times higher than that in neurons [18]. How ascorbic acid leaves astrocytes is still under investigation. The released ascorbic acid is then delivered back into neurons via SVCT2 [2,18]. In the extracellular space between the neutrons and astrocytes, the ascorbic acid concentration is between 200 and 400 μM, while in neurons it is 10 mM and in astrocytes 1 mM [2].
New Understanding of the Nature and Causes of Major Depression
Published in Scott Mendelson, Herbal Treatment of Major Depression, 2019
Neurons do not require insulin to take up glucose. Indeed, the two main glucose transporters in the brain, GLUT1 and GLUT3, have classically been seen as not being responsive to insulin. In turn, it has been assumed that insulin has no important role in brain activity. However, insulin is actively transported into the brain, and insulin receptors are found in a variety of important areas of the brain, particularly the frontal cortex.63 There are also areas of the brain, such as the hippocampus, where insulin-sensitive GLUT4 reside.64 Recent studies have shown that insulin can increase the uptake and metabolism of glucose in the brain.65 Thus, one might expect that insulin resistance would dampen glucose metabolism in the brain and contribute to mood disorder. However, effects of insulin on the cell signaling pathways within the neurons and glial cells of the brain may be more important than effects on glucose metabolism. Indeed, insulin treatment increases the expression of BDNF and its transducer, tropomyosin receptor kinase B (TrkB) receptors in the hippocampi of young rats.66 Another study showed that in the brains of rats made insulin-resistant by high fat diets, insulin no longer fully activated the Akt and mTOR, nor inhibited GSK-3β pathways in the cerebral cortex, which led to decreases in dendritic spine density.67
New insights into the in vitro, in situ and in vivo antihyperglycemic mechanisms of gallic acid and p-coumaric acid
Published in Archives of Physiology and Biochemistry, 2022
Adel Abdel-Moneim, Sanaa M. Abd El-Twab, Ahmed I. Yousef, Mohamed B. Ashour, Eman S. Abdel Reheim, Mennat Allah A. Hamed
Concerning peripheral glucose uptake by rat’s diaphragm in vitro, the present data indicated that GA and PCA exhibited a marked increase of the peripheral glucose consumption as compared to control. This finding suggested that both tested agents may have insulin-mimetic action or non-insulin mediated effects which may contribute to increase expression of both glucose transporters GLUT1 and GLUT3 (Alpert et al.2002). GA enhances insulin-dependent glucose uptake through translocation and activation of GLUT4 in PI3k/p-Akt pathway in epididymal adipose tissue of insulin-resistant animal model (Gandhi et al. 2014). Furthermore, GA stimulates GLUT4 translocation and glucose uptake in an aPKCζ/λ dependent manner in 3T3-L1 cells (Prasad et al. 2010). On the other hand, PCA may activate adenosine monophosphate (AMP)-activated protein kinase (AMPK), an enzyme that regulates energy homeostasis by increasing glucose uptake, β-oxidation of fatty acids and triacylglycerol synthesis. Thus, the activators of AMPK are often used as antidiabetic agents (Pei et al. 2016). In addition, Yoon et al. (2013) concluded that PCA increases the phosphorylation of AMPK, promotes the β-oxidation of fatty acids by increasing the mRNA expression of carnitine palmitoyltransferase-1 (CPT-1) and its transcription factor peroxisome proliferator-activated receptor-α (PPARα), suppresses oleic acid-induced triglyceride accumulation and enhances glucose uptake in L6 skeletal muscle, leading to modulation in glucose and lipid metabolism.
SLC2A3 rs12842 polymorphism and risk for Alzheimer’s disease
Published in Neurological Research, 2020
Stylianos Arseniou, Vasileios Siokas, Athina-Maria Aloizou, Polyxeni Stamati, Alexios-Fotios A. Mentis, Zisis Tsouris, Metaxia Dastamani, Eleni Peristeri, Varvara Valotassiou, Dimitrios P. Bogdanos, Georgios M. Hadjigeorgiou, Efthimios Dardiotis
The brain relies heavily on glucose, as its main energy source. Specific membrane transporters are required in order for hydrophilic substances, such as glucose, to cross the blood-brain barrier (BBB) [20]. Glucose transport is mediated by three families of solute carriers: (a) the Major Facilitator Superfamily (MFS) glucose SLC2 family of facilitated transporters, GLUTs, (b) the SLC5 family of active sodium-driven glucose transporters (SGLTs), and (c) the SLC50 family of uniporters (SWEETs) [21]. The most highly encountered glucose transporters (GLUTs) in the brain are GLUT1 and GLUT3. GLUT1 is the product of the SLC2A1 gene, and it is predominantly expressed in the human erythrocyte membrane, the endothelial cells of the BBB, and astrocytes [22]. GLUT3, on the other hand, is encoded by the SLC2A3 gene, which is specifically expressed in neurons [23], and it is consequently named the neuronal glucose transporter [24]. In the brain, GLUT1 mediates the transport of glucose from circulating blood in the microvasculature to the interstitial fluid [25]. Following the above process, GLUT3 transports glucose from the extracellular space into the neuron [26].
Blood-brain barrier receptors and transporters: an insight on their function and how to exploit them through nanotechnology
Published in Expert Opinion on Drug Delivery, 2019
Rui Pedro Moura, Cláudia Martins, Soraia Pinto, Flávia Sousa, Bruno Sarmento
Glucose transporters (GLUTs) are a group of glycoproteins composed of 12 transmembrane α-helixes, assembled in tags of 3 sharing similar structure. GLUTs possess other two and three extracellular and intracellular helixes, respectively. Similarly to the previously mentioned receptors, after undergoing protein synthesis, these transporters are carried to the endoplasmic reticulum for post-translational modifications, consisting of adequate protein folding, glycosylation, and phosphorylation [74]. The main role of GLUTs is the transport of glucose or other hexose and/or pentose sugars from the blood to the interior of the cell. Thus, GLUTs are expressed in several tissues throughout the body. Since there are many members of the GLUT family, each one of them may have higher or lower expression levels, depending on the biologic site where it is located. In what concerns the brain, it has been described that GLUT1, is mainly expressed in endothelial cells with a considerably high glycosylation percentage, presenting a molecular weight of 55 kDa. Also, GLUT1 is thoroughly expressed in astrocytes and other cellular components of the neurovascular unit, although with a considerably lower rate of glycosylation, holding a molecular weight of 45 kDa. GLUT3 is the main transporter expressed by neurons. The microglia present a wide expression of GLUT5; however, it holds a lower affinity for glucose and a higher affinity towards fructose [75].