AJP - Endocrinology and Metabolism, Vol 268, Issue 5 E820-E824, Copyright © 1995 by American Physiological Society
Chloroquine does not exert insulin-like actions on human forearm muscle metabolism
E. J. Barrett, L. A. Jahn, D. M. Oliveras and D. A. Fryburg
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Insulin's anabolic action on skeletal muscle and whole body protein is
attributable to its action to slow tissue proteolysis. The antimalarial
chloroquine inhibits lysosomal proteolysis and is reported to improve
glycemia in poorly controlled diabetic patients. We infused chloroquine
into the brachial artery of seven healthy postabsorptive volunteers over 3
h during a steady-state infusion of L-[ring-2,6-3H]phenylalanine (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 postabsorptive human skeletal muscle: 1)
lysosomal proteolysis does not make a major contribution to proteolysis;
and 2) chloroquine does not cause an acute increase in glucose uptake.
These findings suggest that the inhibition of postabsorptive muscle protein
degradation provoked by physiological increases in plasma insulin is likely
mediated by a nonlysosomal proteolytic pathway.
