GLUT2 mutations, translocation, and receptor function in diet sugar managing

Abstract

Cloned 20 years ago, GLUT2 is a facilitative glucose transporter in the liver, pancreas, intestine, kidney, and brain. It ensures large bidirectional fluxes of glucose in and out the cell due to its low affinity and high capacity. It also transports other dietary sugars, such as fructose and galactose, within the range of physiological concentrations. Sugars and hormones regulate its gene expression. The contribution of GLUT2 to human metabolic diseases previously appeared modest. However, in the past decade, three major features of the GLUT2 protein have been revealed. First, GLUT2 mutations cause the severe but rare Fanconi-Bickel syndrome, mainly characterized by glycogenosis. Recently, a GLUT2 polymorphism has been associated with preferences for sugary food. Second, the GLUT2 location at the cell surface is regulated; this governs cellular activities dependent on glucose in the intestine and possibly those in the liver and pancreas. For instance, GLUT2 translocation from an intracellular pool to the apical membrane after a sugar meal transiently increases sugar uptake by enterocytes (reviewed in 32). Third, GLUT2 functions as a membrane receptor of sugar. Independently of glucose metabolism, GLUT2 detects the presence of extracellular sugar and transduces a signal to modulate cell functions, including beta-cell insulin secretion, renal reabsorption, and intestinal absorption according to the sugar environment. These recent developments are examined here in heath and metabolic disease, highlighting various unanswered questions.

Diverse roles for theDrosophilafructose sensor Gr43a

“…For example, mammals appear to sense glucose (and other sugars) in the gut using the T1R2/T1R3 taste receptors, 2,3 and the glucose transporter GLUT2 mediates glucose uptake in the pancreas and probably also in selected hypothalamic and other neurons in the brain. 4 These glucose-sensing processes are essential for the regulation of nutrient metabolisms and behaviors via the secretion of insulin, glucagon, and numerous neuropeptides. 5 In insects, the G-protein coupled receptor BOSS was proposed to function as a glucose sensor in the fat body to regulate insulin signaling.…”

Keratin 8 modulates β-cell stress responses and normoglycaemia

“…GLUT2 is abundant in murine b-cells and has a high capacity for glucose uptake. Hence, a significant dysfunction in GLUT2 is required to alter insulin secretion from b-cells (Leturque et al, 2009). This might partly explain the high glucose tolerance and normal basal serum insulin levels, despite GLUT2 mislocalisation in K8…”

Role of nutrient transporters in lifestyle-related diseases

“…GLUT2 is also expressed in the liver and pancreatic beta-cells. Pancreatic GLUT2 regulates glucose influx into the beta-cells on which insulin secretion depends 4) . Hepatic GLUT2 plays an important role in the release of glucose resulting from gluconeogenesis in the liver in response to fasting 4) .…”

“…Pancreatic GLUT2 regulates glucose influx into the beta-cells on which insulin secretion depends 4) . Hepatic GLUT2 plays an important role in the release of glucose resulting from gluconeogenesis in the liver in response to fasting 4) . Insulin can stimulate glucose uptake in the muscle and adipose tissue by an increase in the translocation of GLUT4 from intracellular organelles to the plasma membrane of the cells 5) .…”

“…GLUT2 has a high Km value for glucose and can regulate glucose entry, and may regulate insulin secretion in pancreatic beta-cells 4) . GLUT2 is also expressed in the liver and regulates glucose uptake/efflux, and this transport activity is important to maintain the blood glucose level.…”