title: Chloroquine does not exert insulin-like actions on human forearm muscle metabolism.
abstract: 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.
authors.affiliation: Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Barrett
authors.forename: L A
authors.initials: LA
authors.lastname: Jahn
authors.forename: D M
authors.initials: DM
authors.lastname: Oliveras
authors.forename: D A
authors.initials: DA
authors.lastname: Fryburg
mesh_terms: D000328:Adult; D002738:Chloroquine / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005542:Forearm; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009132:Muscles / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D010649:Phenylalanine / Q000097:blood / Q000493:pharmacokinetics; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D006728:Hormones; D007328:Insulin; D007773:Lactates; D019344:Lactic Acid; D010649:Phenylalanine; D002738:Chloroquine; D005947:Glucose