Biology of human sodium glucose transporters.

  title={Biology of human sodium glucose transporters.},
  author={Ernest M. Wright and Donald D. F. Loo and Bruce A. Hirayama},
  journal={Physiological reviews},
  volume={91 2},
There are two classes of glucose transporters involved in glucose homeostasis in the body, the facilitated transporters or uniporters (GLUTs) and the active transporters or symporters (SGLTs). The energy for active glucose transport is provided by the sodium gradient across the cell membrane, the Na(+) glucose cotransport hypothesis first proposed in 1960 by Crane. Since the cloning of SGLT1 in 1987, there have been advances in the genetics, molecular biology, biochemistry, biophysics, and… 

Structure and mechanism of the SGLT family of glucose transporters.

Cryo-electron microscopy structures of the prototypic human SGLT1 and a related monocarboxylate transporter SMCT1 are reported, providing insights into the multifaceted functions of SGLTs.

Active Glucose Transport 2020 and Beyond

The intestinal glucose cotransporter (SGLT1) was the first to be identified, cloned, and studied in heterologous expression systems such as Xenopus oocytes and cultured cells and is the founding member of the SLC5 human gene family and the large APC superfamily found throughout all life forms.

Glucose transport families SLC5 and SLC50.

  • E. Wright
  • Biology
    Molecular aspects of medicine
  • 2013

Glucose transporters in the mammalian blood cells

Understanding the complexity of glucose homeostasis that includes knowledge about tissue distribution and function of GLUTs, as well as the signaling pathways that regulate glucose metabolism, may help to develop new therapeutic strategies to target specific diseases, such as diabetes mellitus, some autoimmunity diseases, and cancer.

The facilitative glucose transporter GLUT12: what do we know and what would we like to know?

Glucose, one of the most abundant molecules in nature, is used by most of the mammalian cells as their main energy source. Obtained from the diet, glucose is absorbed in the small intestine,

Bridging the gap between structure and kinetics of human SGLT1.

The results establish that glucose and phlorizin occupy the same binding site and that F101 is involved in binding to the phloretin group of the inhibitor, and provide a bridge between kinetics and structural studies of cotransporters.

Inhibitor binding mode and allosteric regulation of Na+-glucose symporters

Structural models of human SGLT1/2 in complex with inhibitors are developed which helps to understand inhibitor subtype selectivity and demonstrates that sub type selectivity arises from Na+-regulated outer gate closure and a variable region in extracellular loop EL5.

Natural Products as Lead Compounds for Sodium Glucose Cotransporter (SGLT) Inhibitors.

The dual SGLT1/SGLT2 inhibitory activity of phlorizin has served as a model for the development and testing of new drugs exhibiting both activities and some other flavonoids and especially flavonoid enriched plant extracts have been investigated for their potency to reduce postprandial blood glucose levels.



The sodium/glucose cotransport family SLC5

The sodium/glucose cotransporter family (SLCA5) has 220 or more members in animal and bacterial cells. There are 11 human genes expressed in tissues ranging from epithelia to the central nervous

Bridging the gap between structure and kinetics of human SGLT1.

The results establish that glucose and phlorizin occupy the same binding site and that F101 is involved in binding to the phloretin group of the inhibitor, and provide a bridge between kinetics and structural studies of cotransporters.

Residue 457 Controls Sugar Binding and Transport in the Na+/Glucose Cotransporter*

Correlation of kinetics with amino acid sequences indicates that residue Gln-457 sequentially interacts with O1 of the pyranose in the binding site, and with O5 in the translocation pathway, suggesting there are at least two steps in the sugar translocation process.

Regulation of Na+/glucose cotransporters.

It is concluded that PKA and PKC regulate rabbit SGLT1 activity by modulating the number of cotransporters in the plasma membrane and that this occurs through regulation of exocytosis and endocytotic.

A Single Amino Acid Change Converts the Sugar Sensor SGLT3 into a Sugar Transporter

It is demonstrated that hSGLT3 functions as a sugar sensor in vivo and that mutating a single amino acid converts this sugar sensor into a sugar transporter similar to SGLT1.

Renal Na(+)-glucose cotransporters.

  • E. Wright
  • Biology
    American journal of physiology. Renal physiology
  • 2001
There are at least three different candidates for these human renal Na(+)-glucose cotransporters, and this review will focus on the structure-function relationships of these three transporers, SGLT1, S GLT2, and SGLt3.

Cation Effects on Protein Conformation and Transport in the Na+/Glucose Cotransporter*

Similarity to the effects of cation substitution in MelB suggests that the mechanism of energy coupling has been evolutionarily conserved and Mathematical simulations suggest that the largest contribution to the kinetic variability of both cation and sugar transport is associated with cation binding.

Sugar Binding to Na/Glucose Cotransporters Is Determined by the Carboxyl-terminal Half of the Protein (*)

It is concluded that recognition/transport of organic substrate is mediated by interactions distal to amino acid 380, while cation binding is determined by interactions arising from the amino- and carboxyl-terminal halves of the transporters.

Assignment of the human Na+/glucose cotransporter gene SGLT1 to chromosome 22q13.1.

A cosmid probe is used for fluorescence in situ hybridization, which refines the localization to 22q13.1, and provides an example of the utility of the SGLT1 probe as a diagnostic for genetic diseases associated with translocations of chromosome 22.

Molecular Characteristics of Na+-coupled Glucose Transporters in Adult and Embryonic Rat Kidney *

It is shown that expression of rat SGLT2 mRNA is kidney specific and that it is strongly and exclusively expressed in proximal tubule S1 segments, which strongly indicate that S GLT2 is the major kidney cortical low affinity glucose transporter.