title: Stereoselective effects of 3-hydroxybutyrate on glucose utilization of rat cardiomyocytes.
abstract: In researches of ketone bodies, D-3-hydroxybutyrate (D-3HB) is usually the major one which has been investigated; in contrast, little attention has been paid to L-3-hydroxybutyrate (L-3HB), because of its presence in trace amounts, its dubious metabolism, and a lack of knowledge about its sources. In the present study we determined the distributions of enantiomers of 3-hydroxybutyrate (3HB) in rat brain, liver, heart, and kidney homogenates, and we found the heart homogenate contained an enriched amount of L-3HB (37.67 microM/mg protein) which generated a significant ratio of 66/34 (D/L). The ratio was altered to be 87/13 in the diabetic rat heart homogenate. We subsequently found this changed ratio of D/L-3HB may contribute to reduce glucose utilization in cardiomyocytes. Glucose utilization by cardiomyocytes with 5 mM of D-3HB was decreased to 61% of the control, but no interference was observed when D-3HB was replaced with L-3HB, suggesting L-3HB is not utilized for the energy fuel as other ketone bodies are. In addition, the reduced glucose utilization caused by D-3HB gradually recovered in a dose-dependent manner with administration of additional L-3HB. The results gave the necessity of taking L-3HB together with D-3HB into account with regard to glucose utilization, and L-3HB may be a helpful substrate for improving inhibited cardiac pyruvate oxidation caused by hyperketonemia.
authors.affiliation: Department of Pharmaceutical Analysis, School of Pharmacy, Taipei Medical University, No. 250, Wu-Hsing St., Taipei 11031, Taiwan, ROC.
authors.forename: Yih-Chiao
authors.initials: YC
authors.lastname: Tsai
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Chou
authors.forename: An-Bang
authors.initials: AB
authors.lastname: Wu
authors.forename: Chien-Ming
authors.initials: CM
authors.lastname: Hu
authors.forename: Chau-Yang
authors.initials: CY
authors.lastname: Chen
authors.forename: Fu-An
authors.initials: FA
authors.lastname: Chen
authors.forename: Jen-Ai
authors.initials: JA
authors.lastname: Lee
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D005947:Glucose; D020155:3-Hydroxybutyric Acid