Changes of glucose transporters in the cerebral adaptation to hypoglycemia

Repeated hypoglycemia increases the glycemic thresholds of responses of cou nterregulatory hormones and of symptoms to subsequent hypoglycemia. This ma y in part be due to cerebral adaptation to hypoglycemia, which involves glu cose transporter-1 (GLUT1) and glucose transporter-3 (GLUT3). To investigat e the role of brain GLUT1 and GLUT3 in cerebral adaptation to chronic hypog lycemia, GLUT1 and GLUT3 mRNA and protein expressions were determined in ra t brain using RT-PCR and Western blot analyses after 4- and 8-day hypoglyce mic insults. Hypoglycemia was induced in rats by twice daily subcutaneous i njection of intermediate-acting insulin with dosage adjustment according to the blood glucose levels. Target level of hypoglycemia (< 2.5 mmol/l) was achieved at least once a day in all rats included. Control rats received sa line injections. Blood glucose levels during the 4 and 8 days of insulin tr eatment were 2.18 +/- 0.12 and 2.68 +/- 0.07 mmol/l, respectively. Followin g the 4 and 8 days of hypoglycemia, GLUT1 mRNA levels did not significantly change. GLUT3 mRNA expressions after the 4 days of hypoglycemia increased by 36.9 +/- 9.4% compared with that in control rats (P = 0.031), but after the 8 days of hypoglycemia, did not change. On Western blot analysis of tot al particulate rat brain membrane, amount of 55-kDa isoform of GLUT1 protei n did not change after 4- and 8-day hypoglycemia (88.1 +/- 4.9% of control, P = 0.240; 92.1 +/- 1.4% of control, P = 0.096, respectively). In contrast , the expression of GLUT3 protein in the 4-day hypoglycemic rats increased by 51.4 +/- 8.4% compared with that in control rats (P = 0.004). After the 8 days of hypoglycemia, the expression also tended to increase by 44.9 +/- 14.4% (P = 0.119). There was an inverse correlation between the amount of G LUT3 protein expression and mean blood glucose levels in 4-day hypoglycemic and control rats (r = - 0.886, P = 0.019). These data suggest that GLUT3 i soform plays a role in the cerebral adaptation to chronic hypoglycemia. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.