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Lithium action on glucose transport in insulin‐resistant rat skeletal muscle: roles of insulin signaling and p38 MAPK
Author(s) -
Macko Antoni Ryszard,
Beneze Alan,
Teachey Mary K.,
Henriksen Erik J.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.990.17
Subject(s) - medicine , insulin , endocrinology , protein kinase b , insulin receptor , glucose transporter , lithium (medication) , phosphorylation , skeletal muscle , glycogen synthase , glucose uptake , chemistry , p38 mitogen activated protein kinases , mapk/erk pathway , biology , insulin resistance , biochemistry
In insulin‐sensitive rat skeletal muscle, lithium activates glucose transport via a mechanism involving p38 mitogen‐activated protein kinase (p38 MAPK). The mechanism underlying lithium action on glucose transport in insulin‐resistant rat skeletal muscle is unknown. We therefore assessed the effects of lithium on basal and insulin‐stimulated glucose transport, insulin signaling (insulin receptor (IR), Akt, and glycogen synthase kinase‐3 (GSK‐3)), and p38 MAPK in soleus muscle from obese Zucker rats. Lithium (10 mM LiCl) increased basal glucose transport by 49% (p<0.05). Lithium did not induce basal IR tyrosine phosphorylation, but did enhance Akt ser473 phosphorylation (40%) and GSK‐3β ser9 phosphorylation (88%). Lithium potentiated insulin action on glucose transport (74%), Akt ser473 phosphorylation (39%), and GSK‐3β ser9 phosphorylation (36%), and elicited robust increases in p38 MAPK phosphorylation both in the absence (100%) or presence (88%) of insulin. Selective inhibition of p38 MAPK (using 10 µM A304000) completely blocked basal activation of glucose transport by lithium, and significantly reduced (42%) the lithium‐induced enhancement of insulin‐stimulated glucose transport. These results indicate that lithium enhances basal and insulin‐stimulated glucose transport and distal insulin signaling in insulin‐resistant skeletal muscle of obese Zucker rats via engagement of p38 MAPK.