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CaMKKα regulates glucose uptake independent of AMPK and Akt signaling in mouse skeletal muscle
Author(s) -
Witczak Carol A,
Fujii Nobuharu,
Hirshman Michael F,
Goodyear Laurie J
Publication year - 2007
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.21.6.a836
Subject(s) - ampk , glucose uptake , skeletal muscle , protein kinase b , amp activated protein kinase , glucose transporter , protein kinase a , medicine , phosphorylation , chemistry , endocrinology , glut4 , kinase , microbiology and biotechnology , biology , insulin , biochemistry
Studies have demonstrated that Ca 2+ /calmodulin‐dependent protein kinase kinases (CaMKKs) are upstream regulators of AMP‐activated protein kinase (AMPK) and Akt. In skeletal muscle, AMPK and Akt have been implicated in the regulation of glucose uptake. We determined whether CaMKKα regulates AMPK, Akt and/or glucose uptake in mouse skeletal muscle. Plasmids containing constitutively active CaMKKα (caCaMKKα) or empty vector were transfected into tibialis anterior muscles by in vivo electroporation. After 2 wks, caCaMKKα was robustly expressed and increased CaMKI (Thr177/180) phosphorylation, an established CaMKK substrate. caCaMKKα increased in vivo [ 3 H]‐2‐deoxyglucose uptake 2.5‐fold, and AMPKα1 and α2 activities 2.5‐fold, suggesting that caCaMKKα may regulate glucose uptake via AMPK. To assess this possibility, glucose uptake was assessed in AMPKα2 inactive mice transfected with caCaMKKα. In AMPKα2 inactive mice, caCaMKKα did not increase AMPKα1 and α2 activities, but did increase glucose uptake 2.5‐fold. Akt (Thr308) phosphorylation was not altered by caCaMKKα. Consistent with these data, in wild‐type mice insulin increased glucose uptake 2.5‐fold, and caCaMKKα plus insulin increased glucose uptake 5‐fold over unstimulated empty vector. Collectively, these results implicate CaMKKα in the regulation of muscle glucose uptake independent of AMPK and Akt signaling. R01AR42238, F32AR051663