Effect of the fatty acid oxidation inhibitor 2-tetradecylglycidic acid (TDGA) on glucose and fatty acid oxidation in isolated rat soleus muscle.
1. The effect of 2-tetradecylglycidic acid (TDGA), a potent, specific inhibitor of long-chain fatty acid oxidation, on fatty acid and glucose oxidation by isolated rat soleus muscle was studied. 2. TDGA inhibited [1-14C]palmitate oxidation by soleus muscle in a concentration-dependent manner. 3. TDGA inhibited the activity of soleus muscle mitochondrial carnitine palmitoyltransferase A (CPT-A). 4. Added palmitate (0.5 mM) significantly inhibited D-[U-14C]glucose oxidation and, under conditions where TDGA inhibited palmitate oxidation, the oxidation of D-[U-14C]glucose by isolated soleus muscle was significantly stimulated. 5. TDGA stimulation of glucose oxidation was reversed by octanoate, a medium-chain fatty acid whose oxidation is not inhibited by TDGA. 6. When nondiabetic rats were treated with TDGA (10 mg/kg p.o./day x 3 days), fasting plasma glucose was significantly lowered and the ability of isolated contralateral soleus muscles to oxidize palmitate was inhibited while glucose oxidation was significantly stimulated.
Tuman
R W
RW
Department of Biological Research, McNeil Pharmaceutical, Spring House, PA 19477.
Joseph
J M
JM
Brentzel
H J
HJ
Tutwiler
G F
GF
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002210:Caprylates / Q000494:pharmacology; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D004852:Epoxy Compounds / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D002210:Caprylates; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D005227:Fatty Acids; D010169:Palmitic Acids; D019308:Palmitic Acid; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose; C031492:octanoic acid; C021756:2-tetradecylglycidic acid