Hypoglycaemia in Clinical Diabetes

156 IMPAIRED AWARENESS OF HYPOGLYCAEMIAFigure 7.7 Rates of brain glucose uptake, epinephrine concentration and total symptoms of hypoglycaemiain non-diabetic subjects before and after prolonged hypoglycaemia. Initial day of investigation(hatched); after 56 hours of hypoglycaemia (solid). ∗ Significant difference from baseline for each ofthe two days. Reproduced from Boyle (1997), Diabetologia, 40, S69–S74. With kind permission ofSpringer Science and Business MediaDuring hypoglycaemia, glucose transport into the brain becomes rate-limiting, and brainenergy metabolism deteriorates. The adaptive response results from an increased utilisationof glucose by the brain. In rodents, the transport of glucose across the blood–brain barrier isincreased after several days of chronic hypoglycaemia (McCall et al., 1986). Further studiesin rats of glucose transport activity across the blood–brain barrier have shown that whenblood glucose was kept below 2.0 mmol/l for several days, changes in expression of theglucose transporter, GLUT-1, in brain microvasculature occurred in response to the chronichypoglycaemia (Kumagai et al., 1995). This increase in GLUT-1 activity was responsiblefor the compensatory increase in glucose transport across the blood–brain barrier.