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Rac1 is a novel regulator of stretch‐induced glucose uptake in muscle
Author(s) -
Sylow Lykke,
Kleinert Maximilian,
Richter Erik A,
Jensen Thomas E
Publication year - 2013
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.27.1_supplement.1152.7
Subject(s) - rac1 , soleus muscle , skeletal muscle , chemistry , glucose uptake , microbiology and biotechnology , phosphorylation , insulin , medicine , endocrinology , biology , biochemistry , signal transduction
Objective The actin‐cytoskeleton‐regulating GTPase Rac1 is required for insulin‐stimulated glucose uptake in cultured muscle cells and is dysregulated in insulin resistant states. We previously found that both insulin and exercise activates Rac1 in mouse and human skeletal muscle, and is required for glucose uptake induced by these stimuli. However, it is unknown whether mechanical stress, which is an integrated component of muscle contraction and increases glucose uptake, activates Rac1. Furthermore, the involvement of Rac1 in stretch‐induced glucose uptake has not been investigated. Methods We examined the involvement of Rac1 in stretch‐stimulated glucose uptake and signalling in incubated soleus and EDL muscles from tetracycline‐inducible muscle‐specific Rac1 knockout mice. Results Passive stretching (15 minutes to 130 mN) increased phosphorylation of Rac1's downstream target, PAKThr423 by ~200% in both soleus and EDL muscles. This response was inhibited by 60% in soleus and 75% in EDL from Rac1 knockout mice. In soleus and EDL, stretch increased 2‐Deoxy‐glucose uptake by 240% and 130%, respectively. This response was decreased in the Rac1 knockout muscles by 30% in soleus and 50% in EDL muscles. Conclusion These data show that Rac1 and its downstream target, PAK1 are activated by stretching and are important regulators of stretch‐stimulated glucose uptake in skeletal muscle.