Increased cerebral glucose utilization and decreased glucose transporter Glut1 during chronic hyperglycemia in rat brain.

Whereas acute hyperglycemia has been shown to result in an unchanged local cerebral glucose utilization (LCGU) the changes of LCGU during chronic hyperglycemia are a matter of dispute. The present study had three aims: (1) To compare the effects of acute and chronic hyperglycemia on LCGU and to investigate in vivo the lactate level as a potential indicator of glycolytic flux. (2) To investigate local changes in brain Glut1 and/or Glut3 glucose transporter densities during chronic hyperglycemia. (3) To analyze the relationship between LCGU and local Glut densities during chronic hyperglycemia. To induce chronic hyperglycemia in rats steptozotocin was given i.p. and experiments were performed 3 weeks later. LCGU was measured by the 2-[14C]deoxyglucose method and intraparenchymal lactate concentration by MR-spectroscopy. Local densities of the glucose transport proteins were determined by immunoautoradiographic methods. During chronic hyperglycemia weighted average of LCGU increased by 13.9% whereas it remained unchanged during acute hyperglycemia. The cerebral lactate/choline ratio was increased by 143% during chronic hyperglycemia. The average density of glucose transporters Glut1 decreased by 7.5%. Local densities of Glut1 were decreased in 12 of 28 brain structures. Glut3 remained unchanged. Positive correlations were found between LCGU and local Glut densities during control conditions and during chronic hyperglycemia. It was concluded that (1) Chronic, but not acute hyperglycemia is followed by an increased LCGU. (2) The capacity to transport glucose is decreased during chronic hyperglycemia. (3) Increased LCGU and decreased densities of Glut1 are matched on a local level.

Increase in glucose transporter densities of Glut3 and decrease of glucose utilization in rat brain after one week of hypoglycemia.

The present study addresses the question whether a chronic decrease of plasma glucose concentration for 1 week induces a global or local increase in glucose transporter densities Glut1 and Glut3 in the brain. To induce chronic hypoglycemia insulin was infused into rats by osmotic minipumps for 1 week resulting in a mean plasma glucose concentration of 3.1+/-0.5 mmol/l (control group: 8.1+/-0.5 mmol/l). Global and local densities of Glut1 and Glut3 glucose transporters were measured by immunoautoradiographic methods. The mean density of glucose transporters Glut1 remained unchanged, whereas the mean density of Glut3 increased slightly, although significantly. To determine whether the increased density of Glut3 is related to a change in glucose metabolism, the local cerebral metabolic rate of glucose (lCMR(glc)) was quantified by the 2-deoxyglucose method. Mean glucose utilization was decreased by 15%. Local analysis of transporter densities (Glut1 and Glut3) and glucose utilization showed a significant correlation between local glucose transporter densities (Glut1 and Glut3) and lCMR(glc) during hypoglycemia as already previously observed during normoglycemia. It is concluded that 1 week of hypoglycemia is a stimulus for the induction of additional glucose transporters Glut3 in the brain. These additional neuronal glucose transporters may support the maintenance of glucose utilization which is not completely maintained under these conditions.