Stimulation of glucose metabolism in human blood cells by inhibitors of carnitine-dependent fatty acid transport.
According to a well accepted hypothesis, increased fatty acid oxidation can lead to hyperglycaemia by stimulating gluconeogenesis and reducing glycolysis. Therefore, inhibitors of fatty acid metabolism should cause hypoglycaemia by inhibiting gluconeogenesis and activating glycolysis. Various substances were tested to validate this hypothesis with regard to glucose oxidation in human mononuclear leukocytes and thrombocytes. 2-(3-Methyl-cinnamyl-hydrazono)-propionate, an inhibitor of the carnitine acyltransfer system was found to cause hypoglycaemia in whole animals and to inhibit gluconeogensis in the perfused guinea pig liver, while the acetyl-CoA/CoASH ratio was decreased. This substance stimulated the metabolism of glucose to CO2 in human mononuclear leukocytes and especially in platelets. This effect could be potentiated if concanavalin A and 2-(3-methyl-cinnamyl-hydrazono)-propionate were applied simultaneously. Under these conditions, however, fatty acid oxidation was no longer inhibited. From these results, it can be concluded that the activation of glucose oxidation by 2-(3-methyl-cinnamyl-hydrazono)-propionate is independent of its effect on fatty acid metabolism. Other inhibitors of fatty acid metabolism which were also investigated behaved similarly.
Haeckel
R
R
Zentralkrankenhaus St. Jürgen-Strasse, Bremen.
Colic
D
D
Binder
L
L
Oellerich
M
M
D001786:Blood Glucose / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002331:Carnitine / Q000502:physiology; D004357:Drug Synergism; D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D002331:Carnitine