Inhibition of mitochondrial carnitine acylcarnitine translocase by hypoglycaemia-inducing substances.
The rate of mitochondrial carnitine-carnitine exchange mediated by carnitine acylcarnitine translocase was measured in the presence of the two hypoglycaemia-inducing drugs, 2-(3-methyl-cinnamyl-hydrazono)-propionate and 2-(3-phenylpropoxyimino)-butyric acid (BM 13.677). Both substances caused a concentration-dependent decrease in the rate of carnitine uptake in guinea pig liver mitochondria. Apparent initial influx rates were decreased by 75% and 80% at a concentration of 2 mmol/l 2-(3-methyl-cinnamyl-hydrazono)-propionate and 2-(3-phenylpropoxyimino)-butyric acid, respectively. Intraperitoneal injections of 212 mumol 2-(3-phenylpropoxyimino)-butyric acid or 21 mumol 2-(3-methyl-cinnamyl-hydrazono)-propionate per kg body weight caused a noticeable decrease in blood glucose concentration. A significant fall of the blood ketone body concentration was achieved with 2-(3-methyl-cinnamyl-hydrazono)-propionate or 2-(3-phenylpropoxyimino)-butyric acid, at dosages of 21 and 255 mumol/l, respectively. Furthermore there was a dose-dependent increase in the plasma free fatty acid concentration in the presence of 2-(3-methyl-cinnamyl-hydrazono)-propionate. This increase, however, was much less pronounced with 2-(3-phenylpropoxyimino)-butyric acid. Metabolic effects of 2-(3-methyl-cinnamyl-hydrazono)-propionate are consistent with an inhibition of long-chain fatty acid transport, whereas an additional mechanism of action has to be assumed for 2-(3-phenylpropoxyimino)-butyric acid.
Beneking
M
M
Institut für Klinische Chemie, Medizinische Hochschule Hannover, FRG.
Oellerich
M
M
Binder
L
L
Choitz
G F
GF
Haeckel
R
R
D000818:Animals; D002331:Carnitine / Q000378:metabolism; D002333:Carnitine Acyltransferases; D055598:Chemical Phenomena; D002621:Chemistry; D002934:Cinnamates / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006168:Guinea Pigs; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007098:Imino Acids / Q000494:pharmacology*; D007657:Ketone Bodies / Q000097:blood; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D014166:Transferases / Q000037:antagonists & inhibitors*
D002934:Cinnamates; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007098:Imino Acids; D007657:Ketone Bodies; C065280:BM 13677; C039804:BM 42304; D014166:Transferases; D002333:Carnitine Acyltransferases; D002331:Carnitine