Effects of lactate on glucose metabolism of developing rat brain.
The effects of hyperlactatemia on cerebral glucose metabolism of normoglycemic 20-day-old rats were studied in animals breathing air or 20% CO2:21% O2:59% N2. Sodium lactate or sodium bicarbonate were given intraperitoneally, together with a mixture of [3H]deoxyglucose and [2-14C]glucose. Animals were sacrificed in a freeze-blowing apparatus at intervals of 2-15 min after injection. Blood lactate levels in the lactate-injected rats were 4-6 mM. Hyperlactatemia caused a gradual decline in the brain rate of glucose utilization in air-breathing animals to 50-70% of control rates. Results with both tracers were similar. Concentrations of Krebs cycle intermediates and glutamate did not decrease. These findings indicate that lactate can partially replace glucose as an oxidative fuel for developing rat brain. Hypercapnia depressed the rate of glucose utilization by developing brain and rates were 30-40% lower still in lactate-injected hypercapnic rats. Decreases in levels of Krebs cycle intermediates and glutamate were similar in both groups. Thus, lactate and CO2 are additive in their depressant effects on brain glucose utilization. The observation that lactate did not prevent the decreases in Krebs cycle intermediates and glutamate caused by hypercapnic acidosis suggests an inhibition of flux through pyruvate dehydrogenase during hypercapnia. The data from this study, coupled with data on lactate transport across the blood-brain barrier, indicate that the direction of movement of lactate and its rate of utilization by developing brain are functions of its concentration on blood relative to brain. Physiological and pathological conditions which elevate blood lactate levels above those in brain will, then, have a sparing effect upon brain glucose utilization.
D000471:Alkalosis / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006935:Hypercapnia / Q000378:metabolism; D007773:Lactates / Q000097:blood / Q000494:pharmacology*; D019344:Lactic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D017693:Sodium Bicarbonate
D001639:Bicarbonates; D001786:Blood Glucose; D007773:Lactates; D019344:Lactic Acid; D017693:Sodium Bicarbonate; D005947:Glucose