LITHIUM INCREASES SUSCEPTIBILITY OF MUSCLE GLUCOSE-TRANSPORT TO STIMULATION BY VARIOUS AGENTS

Lithium is thought to have an insulin-like effect on glucose transport and metabolism in skeletal muscle and adipocytes. However, we found t hat lithium had only a minimal effect on basal glucose transport activ ity in rat epitrochlearis muscles. Instead, lithium markedly increased the sensitivity of glucose transport to insulin, so that the increase in glucose transport activity induced by 300 pM insulin was similar t o 2.5-fold greater in the presence of lithium than in its absence. Lit hium also caused a modest increase in insulin responsiveness. This enh ancement of the susceptibility of the glucose transport process to sti mulation was not limited to insulin, because lithium induced increases in the susceptibility of glucose transport to stimulation by contract ile activity, hypoxia, a phorbol ester, and phospholipase C. Lithium a lso blunted the activation of glycogen phosphorylase by epinephrine. T hese effects were not mediated by inhibition of adenylate cyclase, bec ause neither basal- nor epinephrine-stimulated muscle cAMP concentrati on was affected by Lithium treatment. The effects of lithium on glucos e transport and metabolism in skeletal muscle are strikingly similar t o the persistent effects of exercise. These results support the possib ility that lithium might be useful in the treatment of insulin resista nce in patients with noninsulin-dependent diabetes mellitus.