GLUT

INTRODUCTION:
  • GLUTs are integral membrane proteins that contain 12 membrane-spanning helices with both the amino and carboxyl termini exposed on the cytoplasmic side of the plasma membrane. GLUT proteins transport glucose and related hexoses according to a model of alternate conformation, which predicts that the transporter exposes a single substrate binding site toward either the outside or the inside of the cell.
  • Binding of glucose to one site provokes a conformational change associated with transport, and releases glucose to the other side of the membrane.
  • The inner and outer glucose-binding sites are, it seems, located in transmembrane segments also, the QLS motif located in the seventh transmembrane segment could be involved in the selection and affinity of transported substrate
  • Insulin secretion is decreased by Somatostatin
  • After an overnight fasting, levels of glucose transporters are reduced in Adipocytes, Cardiac muscle & skeletal muscle
  • TYPES:
    Class I
  • Class I comprises the well-characterized glucose transporters GLUT1-GLUT4 
NameDistributionNotes
GLUT1Is widely distributed in fetal tissues. In the adult, it is expressed at highest levels in erythrocytes and also in the endothelial cells of barrier tissues such as the blood–brain barrier. However, it is responsible for the low level of basal glucose uptake required to sustain respiration in all cells.Levels in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels. GLUT1 expression is upregulated in many tumors.
GLUT2Is a bidirectional transporter, allowing glucose to flow in 2 directions. Is expressed by renal tubular cells, liver cells and pancreatic beta cells. It is also present in the basolateral membrane of the small intestine epithelium. Bidirectionality is required in liver cells to uptake glucose for glycolysis, and release of glucose during gluconeogenesis. In pancreatic beta cells, free flowing glucose is required so that the intracellular environment of these cells can accurately gauge the serum glucose levels. All three monosaccharides (glucose, galactose, and fructose) are transported from the intestinal mucosal cell into the portal circulation by GLUT2.Is a high-frequency and low-affinity isoform.
GLUT3Expressed mostly in neurons (where it is believed to be the main glucose transporter isoform), and in the placenta.Is a high-affinity isoform, allowing it to transport even in times of low glucose concentrations.
GLUT4Found in adipose tissues and striated muscle (skeletal muscle and cardiac muscle)Is the insulin-regulated glucose transporter. Responsible for insulin-regulated glucose storage.
Class II comprises:
  •  GLUT5 (SLC2A5), a fructose transporter in enterocytes
  • GLUT7 - SLC2A7 - (SLC2A7), found in the small and large intestine,transporting glucose out of the endoplasmic reticulum
  • GLUT9 - SLC2A9 - (SLC2A9)
  • GLUT11 (SLC2A11)
Class III comprises:
  • withd=""GLUT6 (SLC2A6),
  • GLUT8 (SLC2A8),
  • GLUT10 (SLC2A10),
  • GLUT12 (SLC2A12), and
  • GLUT13, also H+/myoinositol transporter HMIT (SLC2A13), primarily expressed in brain
Exam Question
  • Glucose transporter in myocyte stimulated by insulin is GLUT 4
  • After an overnight fasting, levels of glucose transporters are reduced in Adipocytes, Cardiac muscle & skeletal muscle
  • Insulin stimulated glucose uptake into fat and muscle cells is mediated by GLUT 4.
  • GLUT 4 glucose transporter is present in the skeletal muscle and adipose tissue
  • GLUT 2 glucose transporter present in beta cells
  • Major site for expression of GLUT5 sperm
  • Insulin resistance down-regulates GLUT-4
  • Glucose diffusion in RBC by GLUT I
  • Insulin secretion is decreased by Somatostatin
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