The association of acetyl-L-carnitine with glucose and lipid metabolism in human muscle in vivo: the effect of hyperinsulinemia.
We examined whether hyperinsulinemia is associated with changes in the amount of L-carnitine and acetyl-L-carnitine in the muscle and whether the source of acetyl-coenzyme A (CoA) (glucose or free fatty acids [FFAs]) influences its further metabolism to acetyl-L-carnitine or through tricarboxylic acid in the skeletal muscle of man in vivo. Twelve healthy men (aged 45 +/- 2 years; body mass index, 25.2 +/- 1.0 kg/m2) were studied using a 4-hour euglycemic-hyperinsulinemic clamp (1.5 mU/kg/min) and indirect calorimetry. Although the mean muscle free L-carnitine and acetyl-L-carnitine concentrations remained unchanged during hyperinsulinemia in the group as a whole, the individual changes in muscle free L-carnitine and acetyl-L-carnitine concentrations were inversely related (r = -.72, P < .02). The basal level of acetyl-L-carnitine was inversely related to the rate of lipid oxidation (r = -.70, P < .02). In a stepwise linear regression analysis, 77% of the variation in the change of acetyl-L-carnitine concentrations was explained by the basal muscle glycogen level (inversely) and nonoxidative glucose disposal rate (directly) during hyperinsulinemia (P < .001); by adding the final FFA concentration (inverse correlation) to the model, 88% of the variation was explained (P < .001). In conclusion, (1) hyperinsulinemia does not enhance skeletal muscle free L-carnitine or acetyl-L-carnitine concentrations in-man, and (2) the acetyl group of acetyl-L-carnitine in human skeletal muscle in vivo is probably mostly derived from glucose and not through beta-oxidation from fatty acids.
Ebeling
P
P
Department of Medicine, Helsinki University Hospital, Finland.
Tuominen
J A
JA
Arenas
J
J
Garcia Benayas
C
C
Koivisto
V A
VA
D000105:Acetyl Coenzyme A / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D000108:Acetylcarnitine / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D000328:Adult; D002153:Calorimetry, Indirect; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D016014:Linear Models; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D010084:Oxidation-Reduction
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D000108:Acetylcarnitine; D000105:Acetyl Coenzyme A; D006003:Glycogen; D005947:Glucose