Beta-hydroxybutyrate reverses insulin-induced hypoglycemic coma in suckling-weanling mice despite low blood and brain glucose levels.
In normal suckling-weanling mice, DL-beta-hydroxybutyrate (30 mmol/kg ip) stimulated insulin secretion and reduced plasma glucose levels. In the brains of these animals, glucose levels were tripled due to a reduced rate of glucose utilization (determined by deoxyglucose phosphorylation). Other metabolite changes were compatible with inhibition of hexokinase, phosphofructokinase, glyceraldehyde-P-dehydrogenase, and pyruvate dehydrogenase activities. In contrast to the decrease in cerebral glycolysis, metabolite changes were compatible with an increase in the Krebs citric acid metabolic flux. The brain energy charge was also elevated. While it is generally believed that ketone bodies cannot sustain normal brain metabolism and function in the absence of glucose, DL-beta-hydroxybutyrate (20 or 30 mmol/kg ip) reversed insulin (100 U/kg sc)-induced hypoglycemia despite the persistence of a critically reduced plasma glucose concentration and near-zero brain glucose levels. Metabolic correlates of possible significance in the behavioral recovery from coma were reductions of the elevated levels of brain aspartate to below normal and ammonia levels to normal. Levels of acetyl CoA were unchanged both before and after treatment with beta-hydroxybutyrate.
Thurston
J H
JH
Washington University School of Medicine, Department of Pediatrics, Children's Hospital, St. Louis, Missouri 63110.
Hauhart
R E
RE
Schiro
J A
JA
D020155:3-Hydroxybutyric Acid; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D006885:Hydroxybutyrates / Q000627:therapeutic use*; D007003:Hypoglycemia / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage*; D051379:Mice; D013997:Time Factors
D000596:Amino Acids; D001786:Blood Glucose; D006885:Hydroxybutyrates; D007328:Insulin; D020155:3-Hydroxybutyric Acid