Anzeige
Erschienen in:
01.04.2007 | Article
Carnitine revisited: potential use as adjunctive treatment in diabetes
Erschienen in: Diabetologia | Ausgabe 4/2007
Einloggen, um Zugang zu erhaltenAbstract
Aims/hypothesis
This study examined the efficacy of supplemental l-carnitine as an adjunctive diabetes therapy in mouse models of metabolic disease. We hypothesised that carnitine would facilitate fatty acid export from tissues in the form of acyl-carnitines, thereby alleviating lipid-induced insulin resistance.
Materials and methods
Obese mice with genetic or diet-induced forms of insulin resistance were fed rodent chow ± 0.5% l-carnitine for a period of 1–8 weeks. Metabolic outcomes included insulin tolerance tests, indirect calorimetry and mass spectrometry-based profiling of acyl-carnitine esters in tissues and plasma.
Results
Carnitine supplementation improved insulin-stimulated glucose disposal in genetically diabetic mice and wild-type mice fed a high-fat diet, without altering body weight or food intake. In severely diabetic mice, carnitine supplementation increased average daily respiratory exchange ratio from 0.886 ± 0.01 to 0.914 ± 0.01 (p < 0.01), reflecting a marked increase in systemic carbohydrate oxidation. Similarly, under insulin-stimulated conditions, carbohydrate oxidation was higher and total energy expenditure increased from 172 ± 10 to 210 ± 9 kJ kg fat-free mass−1 h−1 in the carnitine-supplemented compared with control animals. These metabolic improvements corresponded with a 2.3-fold rise in circulating levels of acetyl-carnitine, which accounts for 86 and 88% of the total acyl-carnitine pool in plasma and skeletal muscle, respectively. Carnitine supplementation also increased several medium- and long-chain acyl-carnitine species in both plasma and tissues.
Conclusions/interpretation
These findings suggest that carnitine supplementation relieves lipid overload and glucose intolerance in obese rodents by enhancing mitochondrial efflux of excess acyl groups from insulin-responsive tissues. Carefully controlled clinical trials should be considered.