CONTROL OF MALONYL-COA BY GLUCOSE AND INSULIN IN PERFUSED SKELETAL-MUSCLE

This study was designed to determine the effects of glucose and insuli n on malonyl-CoA, the potent inhibitor of carnitine palmitoyltransfera se I, in the gastrocnemius/plantaris muscle group. Isolated rat hindli mbs were perfused with Krebs-Henseleit bicarbonate buffer containing f resh erythrocytes (hematocrit = 41) and albumin in a flow-through mode for 60 min. Two experiments were performed. In the first, hindlimbs w ere perfused with medium containing no glucose and no insulin (n = 9) or with medium containing 10 mM glucose and 100 muU/ml of insulin (n = 9). Gastrocnemius/plantaris malonyl-CoA was 0.6 +/- 0.1 nmol/g in the absence of glucose and insulin vs. 1.4 +/- 0.1 nmol/g when both gluco se and insulin were added. In the second experiment, hindlimbs were pe rfused with medium containing 10 mM glucose alone, 200 muU insulin alo ne, or with a combination of 10 mM glucose and 200 muU/ml of insulin ( n = 8 for each). Malonyl-CoA was decreased in gastrocnemius/plantaris perfused with glucose alone (0.7 +/0. 2 nmol/g) and with insulin alone (0.7 +/- 0.1 nmol/g) compared with hindlimbs perfused with the combin ation of glucose and insulin (1.4 +/- 0.2 nmol/g). We conclude that bo th glucose and insulin are required for preventing a decline in muscle malonyl-CoA.