REDUCED EFFECTS OF L-CARNITINE ON GLUCOSE AND FATTY-ACID METABOLISM IN MYOCYTES ISOLATED FROM DIABETIC RATS

Depressed glucose utilization and over-reliance of muscle tissues on f at represents a major metabolic disturbance in diabetes. This study wa s designed to investigate the relationship between fatty acid oxidatio n and glucose utilization in diabetic hearts and to examine the role o f L-Carnitine on the utilization of these substrates in diabetes. (CO2 )-C-14 release from [1-C-14]pyruvate (an index of PDH activity), [2-C- 14]pyruvate and [6-C-14]glucose fan index of acetyl-CoA flux through t he Krebs cycle), [U-C-14]glucose (an index of both PDH and acetyl-CoA flux through the Krebs cycle), and [1-C-14]palmitate oxidation were st udied in cardiac myocystes isolated from normal and streptozotocin-inj ected rats. Palmitate oxidation was increased twofold in diabetic myoc ytes 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 pa lmitate oxidation (60-70%) in normal cells but had no effect on diabet ic cells, The activity of PDH and acetyl-CoA flux through the Krebs cy cle 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 acetylcarnit ine, a by-product of PDH activity was also much lower in diabetic cell s than in normal cells but had no effect in diabetes. L-Carnitine also had no effect on (CO2)-C-14 release from [U-C-14]glucose but signific antly decreased that from [6-C-14]glucose, which reflects oxidative me tabolism suggesting that L-Carnitine decreases oxidative glucose utili zation, Thus, these data suggest that the over reliance on fat in diab etes may be in part secondary to a reduction of carbohydrate-generated acetyl-CoA through the Krebs cycle.