Loss of sugar detection by GLUT2 affects glucose homeostasis in mice.
BACKGROUND
Mammals must sense the amount of sugar available to them and respond appropriately. For many years attention has focused on intracellular glucose sensing derived from glucose metabolism. Here, we studied the detection of extracellular glucose concentrations in vivo by invalidating the transduction pathway downstream from the transporter-detector GLUT2 and measured the physiological impact of this pathway.


RESULTS
We produced mice that ubiquitously express the largest cytoplasmic loop of GLUT2, blocking glucose-mediated gene expression in vitro without affecting glucose metabolism. Impairment of GLUT2-mediated sugar detection transiently protected transgenic mice against starvation and streptozotocin-induced diabetes, suggesting that both low- and high-glucose concentrations were not detected. Transgenic mice favored lipid oxidation, and oral glucose was slowly cleared from blood due to low insulin production, despite massive urinary glucose excretion. Kidney adaptation was characterized by a lower rate of glucose reabsorption, whereas pancreatic adaptation was associated with a larger number of small islets.


CONCLUSIONS
Molecular invalidation of sugar sensing in GLUT2-loop transgenic mice changed multiple aspects of glucose homeostasis, highlighting by a top-down approach, the role of membrane glucose receptors as potential therapeutic targets.
Stolarczyk
Emilie
E
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris6, UMR S 872, Paris, France.
Le Gall
Maude
M
Even
Patrick
P
Houllier
Anne
A
Serradas
Patricia
P
Brot-Laroche
Edith
E
Leturque
Armelle
A
D000818:Animals; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D050356:Lipid Metabolism; D051379:Mice; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D010179:Pancreas / Q000502:physiology
D051273:Glucose Transporter Type 2; C495682:Slc2a2 protein, mouse; D005947:Glucose