CHLOROQUINE DOES NOT EXERT INSULIN-LIKE ACTIONS ON HUMAN FOREARM MUSCLE METABOLISM

Insulin's anabolic action on skeletal muscle and whole body protein is attributable to its action to slow tissue proteolysis. The antimalari al chloroquine inhibits lysosomal proteolysis and is reported to impro ve glycemia in poorly controlled diabetic patients. We infused chloroq uine into the brachial artery of seven healthy postabsorptive voluntee rs over 3 h during a steady-state infusion of L-[ring-2,6-H-3]phenylal anine (Phe) to study its effect on muscle glucose and protein turnover . Compared with basal, chloroquine increased forearm blood flow (P < 0 .01) but did not change glucose uptake or lactate release. Neither Phe released from muscle by proteolysis (78 +/- 15 vs. 94 +/- 16 nmol Phe . min(-1). 100 ml(-1)) nor Phe balance (-37 +/- 7 vs. -50 +/- 6 nmol . min(-1). 100 ml(-1)) was reduced from basal. We conclude that in pos tabsorptive human skeletal muscle: 1) lysosomal proteolysis does not m ake a major contribution to proteolysis; and 2) chloroquine does not c ause an acute increase in glucose uptake. These findings suggest that the inhibition of postabsorptive muscle protein degradation provoked b y physiological increases in plasma insulin is likely mediated by a no nlysosomal proteolytic pathway.