Open AccessAntiketogenic and hypoglycemic effects of aminocarnitine and acylaminocarnitines.
Author(s) -
Deborah L. Jenkins,
Owen W. Griffith
Publication year - 1986
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.83.2.290
Subject(s) - carnitine , in vivo , carnitine palmitoyltransferase i , chemistry , medicine , endocrinology , in vitro , beta oxidation , oral administration , carnitine o palmitoyltransferase , pharmacology , fatty acid , biochemistry , biology , microbiology and biotechnology
DL-Aminocarnitine (DL-3-amino-4-trimethylaminobutyrate) is a potent, noncovalent inhibitor of carnitine palmitoyltransferase (palmitoyl-CoA:L-carnitine O-palmitoyltransferase, EC 2.3.1.21). Here we show that decanoyl-DL-aminocarnitine and palmitoyl-DL-aminocarnitine inhibit carnitine palmitoyltransferase in vitro about 7-fold and 100-fold more effectively than does aminocarnitine. Aminocarnitine and its decanoyl and palmitoyl derivatives are active in vivo following oral or parenteral administration and, at doses of 0.3 mmol/kg or less, inhibit the oxidation of [14C]palmitate to 14CO2 by 45-70% in mice. Larger doses do not significantly increase the extent of inhibition, a finding suggesting that substantial carnitine palmitoyltransferase-independent long-chain fatty acid oxidation may occur in vivo. Small doses of aminocarnitine and palmitoylaminocarnitine prevent the development of ketoacidemia in fasted, normal mice and reverse the ketoacidemia observed in diabetic mice. Aminocarnitine has a strong hypoglycemic effect in fasted diabetic mice; a single dose (0.3 mmol/kg) normalizes plasma glucose levels within 4-8 hr and remains effective for at least 12 hr.