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DOI: 10.1055/s-2007-979071
© Georg Thieme Verlag Stuttgart · New York
Reduced Effects of L-Carnitine on Glucose and Fatty Acid Metabolism in Myocytes Isolated From Diabetic Rats
Publication History
1997
1997
Publication Date:
23 April 2007 (online)
Depressed glucose utilization and over-reliance of muscle tissues on fat represents a major metabolic disturbance in diabetes. This study was designed to investigate the relationship between fatty acid oxidation and glucose utilization in diabetic hearts and to examine the role of L-Carnitine on the utilization of these substrates in diabetes. 14CO2 release from [1-14C]pyruvate (an index of PDH activity), [2-14C]pyruvate and [6-14C]glucose (an index of acetyl-CoA flux through the (rebs cycle), [U-14C]glucose (an index of both PDH and acetyl-CoA flux through the Krebs cycle), and [1-14C]palmitate oxidation were studied in cardiac myocystes isolated from normal and streptozotocin-injected rats. Palmitate oxidation was increased twofold in diabetic myocytes compared to normal cells (5.4 ± 1.45 vs 2.35 ± 0.055 nmol/mg protein/30 min, p < 0.05). L-Carnitine (5 mM) significantly increased palmitate oxidation (60-70%) in normal cells but had no effect on diabetic cells. The activity of PDH and acetyl-CoA flux through the Krebs cycle was severely depressed in diabetes (58.14 ± 20.27 and 8.63 ± 0.62 in diabetes vs 128.75 ± 11.47 and 24.84 ± 7.81 nmol/mg protein/30 min in controls, p < 0.05, respectively). The efflux of acetylcarnitine, a by-product of PDH activity was also much lower in diabetic cells than in normal cells but had no effect in diabetes. L-Carnitine also had no effect on 14CO2 release from [U-14C]glucose but significantly decreased that from [6-14C]glucose, which reflects oxidative metabolism suggesting that L-Carnitine decreases oxidative glucose utilization. Thus, these data suggest that the overreliance on fat in diabetes may be in part secondary to a reduction of carbohydrate-generated acetyl-CoA through the Krebs cycle.
Key words
L-Carnitine - Pyruvate dehydrogenase - Fatty acid oxidation - Diabetes - Glucose metabolism