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

Whereas acute hyperglycemia has been shown to result in an unchanged local cerebral glucose utilization (LCGU) the changes of LCGU during chronic hype rglycemia 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 inve stigate in vivo the lactate level as a potential indicator of glycolytic fl ux. (2) To investigate local changes in brain Glut1 and/or Glut3 glucose tr ansporter densities during chronic hyperglycemia. (3) To analyze the relati onship between LCGU and local Glut densities during chronic hyperglycemia. To induce chronic hyperglycemia in rats steptozotocin was given i.p. and ex periments were performed 3 weeks later. LCGU was measured by the 2 - [C-14] deoxyglucose method and intraparenchymal lactate concentration by MR-spectr oscopy. Local densities of the glucose transport proteins were determined b y immunoautoradiographic methods. During chronic hyperglycemia weighted ave rage of LCGU increased by 13.9% whereas it remained unchanged during acute hyperglycemia. The cerebral lactate/choline ratio was increased by 143% dur ing chronic hyperglycemia. The average density of glucose transporters Glut 1 decreased by 7.5%. Local densities of Glut1 were decreased in 12 of 28 br ain 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 hyp erglycemia 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. (C) 2000 Elsevie r Science B.V. All rights reserved.