The Effect of Lithium Chloride on the Distal Insulin Signaling Cascade and on p38 MAPK in the Soleus Muscle of Female Lean Zucker Rats

Abstract

This project focused on determining the effect of lithium on glucose uptake, glycogen synthesis, and insulin signaling proteins, protein kinase B (Akt1) and GSK-3, in isolated soleus muscle from female lean Zucker rats. We also investigated the role of the stress-activated p38 MAPK in the action of lithium to activate skeletal muscle glucose transport. In the absence of insulin, lithium (10 mM LiCl) increased basal glucose transport by 62% (p<0.05) and glycogen synthesis by 112%. Lithium did not alter phosphorylation of Akt ser473, but enhanced GSK-3β ser9 phosphorylation by 41%. Lithium further enhanced the effect of insulin on glucose transport (42%), glycogen synthesis (44%), and GSK-3ß phosphorylation (13%). Lithium increased phosphorylated p38 MAPK 31% without and 19% with insulin. Moreover, a selective p38 MAPK inhibitor, A304000, completely prevented the lithium-induced enhancement of glucose transport revealing the critical involvement of p38 MAPK phosphorylation in lithium-induced glucose transport in isolated skeletal muscle.