GLUT2, glucose sensing and glucose homeostasis

Abstract

The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism. GLUT2 expression is nevertheless required for the physiological control of glucose-sensitive genes, and its inactivation in the liver leads to impaired glucose-stimulated insulin secretion, revealing a liver-beta cell axis, which is likely to be dependent on bile acids controlling beta cell secretion capacity. In the nervous system, GLUT2-dependent glucose sensing controls feeding, thermoregulation and pancreatic islet cell mass and function, as well as sympathetic and parasympathetic activities. Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion. In humans, inactivating mutations in GLUT2 cause Fanconi-Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes. Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. Individuals with a missense mutation in GLUT2 show preference for sugar-containing foods. We will discuss how studies in mice help interpret the role of GLUT2 in human physiology.

Ionic imbalance, in addition to molecular crowding, abates cytoskeletal dynamics and vesicle motility during hypertonic stress

“…S3A), possibly reflecting high cell-surface expression of glucose transporter GLUT2 (Fig. S1E), whose high transport capacity allows faster equilibration of extracellular and intracellular glucose (45). In primary and cultured hepatocytes, another glucose-transporting cell type, the effects of glucose on endosome motility were significantly stronger than those observed in pancreatic β cells ( Fig.…”

Glial hypothalamic inhibition of GLUT2 expression alters satiety, impacting eating behavior

“…Due to its kinetic properties and tissue localization, GLUT2 is involved in the glucosensing mechanism as it has a uniquely low affinity for glucose (Km ∼17 mM) and can also use mannose, galactose, and fructose as low affinity substrates for transport (Thorens, Guillam, Beermann, Burcelin, & Jaquet, 2000). GLUT2 is the major glucose transporter present in hepatocytes, enterocytes, kidney epithelial cells, and cells of the hepatoportal vein (Thorens, 2015). GLUT2 is also the major glucose transporter in pancreatic ß‐cells, where its genetic inactivation impairs glucose uptake and suppresses glucose‐stimulated insulin secretion.…”

The Effect of Ethanolic Extract of Urtica dioica Leaves on High Levels of Blood Glucose and Gene Expression of Glucose Transporter 2 (Glut2) in Liver of Alloxan-Induced Diabetic Mice

“…Glucose transporter 2 (GLUT2) is a membrane protein that facilitates the transport of glucose over a plasma membrane (9). Expression of the GLUT2 protein has been reported in cell membranes of the liver, pancreas, small intestine and to a lesser extent brain and kidney tissues (9).…”

“…Expression of the GLUT2 protein has been reported in cell membranes of the liver, pancreas, small intestine and to a lesser extent brain and kidney tissues (9). It has been shown that the GLUT2 is the major glucose transporter in the plasma membrane of hepatocytes for glucose uptake.…”

“…It has been shown that the GLUT2 is the major glucose transporter in the plasma membrane of hepatocytes for glucose uptake. This protein is also involved in the second step of trans-epithelial glucose transport in the small intestine and the proximal convoluted tubule of kidneys (9).…”