Carbohydrates found in dietary food is absorbed in blood stream in the form of glucose, it involves as a major energy producing source among the organic molecules (Sindhuri Pragallapati, 2019). Glucose is prominent in metabolism which is a major energy source for mammalian cells, they are absorbed in small intestine and stored in the form glycogen in muscle and liver tissues. Glucose is hydrophilic in nature and also there constituted with phospholipid bilayer, so there is chanceless to diffuse across the molecule of hydrophobic plasma membrane. They require a protein named solute carrier (SLC) to assist in transferring in specific way or without employing any adenosine triphosphate (ATP), away from a concentration gradient. The two SLC proteins are facilitative transporters and secondary active transporters act as essential membrane transporter protein prevalent in membranes of organelles and cell surfaces (Jafri et al., 2023, Pujol-Giménez et al., 2013). These transporters are classified to three major classes includes sodium-independent glucose transporters (SLC2) which are commonly said to be a glucose transporters (GLUTs), sodium-dependent glucose transporter (SLC5) and SLC50A is a gene which is also a carrier of glucose transporter protein which code as SWEET protein as shown in a Fig. 1 (Pliszka and Szablewski, 2021, Wright, 2013).

Sodium-independent glucose transporters are facilitative membrane transporters in which GLUTs proteins and SLC2A (Solute carrier) genes are involved. The 14 SLC2 genes have 65 sub family which encode proteins that are also sub-classified into GLUT (glucose transport) proteins organized into 1–3 phylogenetically separate classes (Holman, 2020). With 12 trans-membranes (TMs), it is undoubtedly helping to facilitate the transport of glucose across cell membranes. domains, so called as they span the cell membrane 12 times. GLUTs commonly have amino (ie., N-terminal) and carboxyl (ie., C-terminal) terminals located intracellularly. All the proteins in (major facilitator superfamily) MFS superfamily have RXGRR motifs, which are connected to the catalytic conformational change that takes place throughout facilitated transport. In addition, there is structural pseudosymmetry where the N-terminal is half (TM1–6) and the C-terminal is half (TM7–12) are mirrored, with a large cytoplasmic loop separating the two half proteins (Holman, 2020). In the case of concentration gradient, GLUTs protein family transport glucose in a bidirectional manner (Navale and Paranjape, 2016, Pliszka and Szablewski, 2021). Hexose is a physiological substrate for GLUTs, other alternative substrates for GLUTs includes urate, myo-inositol, and dehydro-ascorbate (Holman, 2020). Various isoforms have varying degrees of affinity for glucose, indicating their ability to adapt to the distinct metabolic necessity in each individual cells.

Hexose transport inside and out of cells was initially assumed to be catalysed by all the GLUT proteins. It is apparent that this is applicable for the class 1 GLUT proteins. In the circumstance of GLUT proteins of classes 2 and 3, it does not have primary catalytic functions, It always has a significant impact on the transporting glucose via catalysis. They may often demonstrate to catalyse the absorption of glucose in experimental systems. They are separated into 14 different membrane GLUTs and grouped into three different classes, Class I (GLUT 1 to 4 and 14), Class II (GLUT5,7 and 9) and Class III (GLUT6, 8, 10, 12, and 13) based on their sequencing similarities through phylogenetic analysis discussed in Table 1. (Holman, 2020, Navale and Paranjape, 2016, Pliszka and Szablewski, 2021, Pujol-Giménez et al., 2013, Shah et al., 2012, Sindhuri Pragallapati1, 2019). GLUT1 is linked to the hormone-regulated, bidirectional transport of glucose in hepatocytes, including thyroid hormone (Navale & Paranjape, 2016). As a D-glucose carrier, GLUT1 was initially isolated through the erythrocyte membrane in 1977. Subsequent research revealed that GLUT1 had a poor affinity for mannose, galactose, glucosamine, and decreased (Zezina, Sercan-Alp, Herrmann, & Biesemann, 2020). High affinity and high-capacity transporter GLUT2 are widely expressed in the pancreatic β-cells and liver are the main organs where it functions as a glucose sensor GLUT2 is expressed. Though expressed on the sinusoidal membrane of hepatocytes, GLUT2 is hypothesized to be involved in the glucose-sensing process in β-cells and to facilitate the bi-directional transport of glucose under hormonal regulation in the liver. Brain tissue is the primary location of GLUT3. Its ability to transport glucose into cells with a greater need for glucose is consistent with its high affinity for the compound. The skeletal muscle, heart, Brain and adipose tissues are all includes the insulin-responsive glucose transporter GLUT 14. It is found in vesicles within the cytoplasm of cells, and insulin causes it to move from there to the plasma membrane. The recruitment of GLUT4 in reaction to insulin, causes an increase in 10- to 20-fold in the transporting glucose (Navale & Paranjape, 2016). The primary functions of GLUT5’s roles is the small intestine’s direct absorption of fructose and the same sugar is retrieved from the glomerular filter present in kidney. In brain of human the GLUT5 involves in immunolabeling and act as a well-defined marker (Jurcovicova, 2014). GLUT11 shares 42% similar sequence homology with fructose transporter GLUT5 (Navale & Paranjape, 2016). In the case of maintaining a controlled distribution of metabolites (like glucose) to tissues, GLUT expression must be controlled to avoid clinical issues such as type 2 diabetes, cancer, and various tissue disorders related to tissue-specific GLUT protein profiles are triggered by or attributed to pathophysiological anomalies in GLUT proteins (Holman, 2020).

Sodium-dependent glucose transporters or also commonly said to be sodium–glucose linked transporter (SGLT) are secondary active transporters, this co transporter of glucose carries SLC5 human genome. The co-transporter SGLT family differs from GLUT family, it consists of membrane-spanning monomer proteins with a single N-glycosylation site and 14 transmembrane domains. SGLTs simultaneously move Na+ ions and glucose and galactose along a concentration gradient. The COOH and NH2 terminals of each of its 14 transmembrane helices face the extracellular environment. In SGLT family each protein ranges between 60–80 k Da and comprise 580–718 amino acids (Navale and Paranjape, 2016, Wright, 2013). The members of SLC5 family coded gene and their tissue localization is arranged in Table 2 (Navale and Paranjape, 2016, Pliszka and Szablewski, 2021, Shah et al., 2012, Wright, 2013).

Transporter which is reported recently known as SLC50, or Sugars Will Eventually be Exported Transporters (SWEET), are extensively distributed in plants and are involved in the physiological movement of sugars along concentration gradients across cell membranes (Jafri et al., 2023, Li-Qing et al., 2010). This transporter protein first found and potentially expressed in Arabidopsis thaliana genes that code for HEK293T cells with polytopic membrane proteins, and a fluorescent intracellular glucose involved as a sensor for monitoring glucose transport. Only one member, SLC50 gene in human genome coded, SLC50A1 is the novel SWEET family of glucose uniporters. The SWEETs are usually appearing in plants, where pathogens and symbionts target them for feeding and they are believed to oversee sugar efflux (Li-Qing et al., 2010, Wright, 2013). Unlike 12 and 14 membrane protein of GLUTs and SGLTs the SWEET is a type of class transporters are assumed that they have 7 no. of transmembrane helices. In transporting sugar, the SWEET protein does not require an environmental pH range, also over the gradient of sugar concentration, these proteins transport the sugar from inside the cells and into the extracellular environment or from the extracellular to intracellular membranes. The ends of N- and C- terminals are situated intracellularly in the proteins consist of each six, transmembrane domains with 12-helices (Ji et al., 2022, Wright, 2013).

The regulation and the control of glucose transport into cells, along with the hormones’ mode of action, differs throughout tissues and organs and during their development, they also divers based on their necessity in metabolic activity (Carbá & Guarner, 2010). GLUTs family, expressed mostly on β cells and other tissues where glucose concentrations are high in the specific organs (Brain, kidney, lungs, muscles, glands, liver and pancreas) follows are detailed in discussion on their physiological and functions are enrolled in this chapter, which has a relatively high glucose transport activity (Sun, Chen, Xue, Li, & Fu, 2023).