title: Brain glucose levels are elevated in chronically hyperglycemic diabetic rats: no evidence for protective adaptation by the blood brain barrier.
abstract: Recent evidence suggests that brain function may be impaired by prolonged elevations of blood glucose, such as those that occur in poorly controlled diabetes. However, little is known about the effects of such hyperglycemia on brain metabolic substrate levels. Using microdialysis in awake, freely moving rats, we directly measured brain extracellular fluid (ECF) glucose, lactate, and beta-hydroxybutyrate (betaOHB) levels in the inferior colliculus in chronically hyperglycemic BB/wor diabetic rats and in control (Sprague-Dawley) rats during euglycemia and acute hyperglycemia. The ECF:plasma glucose ratio (0.27 to 0.34) was remarkably similar in animals from all 3 groups, resulting in proportional elevations of brain ECF glucose in the hyperglycemic groups. Moreover, brain ECF levels of lactate and beta-OHB were increased in diabetic (DM) rats as compared with controls. Our results suggest that no significant protective adaptation of the blood brain barrier (BBB) transfer of glucose occurs in chronic hyperglycemia. Hence, brain tissue may be chronically exposed to markedly elevated levels of glucose and other metabolic fuels during poorly controlled diabetes, and therefore it may be subject to the same long-term adverse effects of hyperglycemia seen in peripheral tissues.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Jacob
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.forename: M L
authors.initials: ML
authors.lastname: Evans
authors.forename: J
authors.initials: J
authors.lastname: Dziura
authors.forename: R S
authors.initials: RS
authors.lastname: Sherwin
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000208:Acute Disease; D000222:Adaptation, Physiological; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002908:Chronic Disease; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000150:complications* / Q000378:metabolism*; D007245:Inferior Colliculi / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D051381:Rats; D011913:Rats, Inbred BB; D017207:Rats, Sprague-Dawley
chemical_list: D019344:Lactic Acid; D005947:Glucose; D020155:3-Hydroxybutyric Acid