Constitutively active CaMKKα stimulates skeletal muscle glucose uptake in insulin-resistant mice in vivo.
Constitutively active CaMKKα stimulates skeletal muscle glucose uptake in insulin-resistant mice in vivo.
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DOI：
10.2337/db13-0452
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发表时间：
2014-01
期刊：
影响因子：
7.7
通讯作者：
Witczak CA
中科院分区：
文献类型：
--
作者：
Hinkley JM;Ferey JL;Brault JJ;Smith CA;Gilliam LA;Witczak CA
In insulin-sensitive skeletal muscle, the expression of constitutively active Ca2+/calmodulin-dependent protein kinase kinase α (caCaMKKα) stimulates glucose uptake independent of insulin signaling (i.e., Akt and Akt-dependent TBC1D1/TBC1D4 phosphorylation). Our objectives were to determine whether caCaMKKα could stimulate glucose uptake additively with insulin in insulin-sensitive muscle, in the basal state in insulin-resistant muscle, and if so, to determine whether the effects were associated with altered TBC1D1/TBC1D4 phosphorylation. Mice were fed a control or high-fat diet (60% kcal) for 12 weeks to induce insulin resistance. Muscles were transfected with empty vector or caCaMKKα plasmids using in vivo electroporation. After 2 weeks, caCaMKKα protein was robustly expressed. In insulin-sensitive muscle, caCaMKKα increased basal in vivo [3H]-2-deoxyglucose uptake approximately twofold, insulin increased glucose uptake approximately twofold, and caCaMKKα plus insulin increased glucose uptake approximately fourfold. caCaMKKα did not increase basal TBC1D1 (Ser237, Thr590, Ser660, pan-Thr/Ser) or TBC1D4 (Ser588, Thr642, pan-Thr/Ser) phosphorylation. In insulin-resistant muscle, caCaMKKα increased basal glucose uptake approximately twofold, and attenuated high-fat diet–induced basal TBC1D1 (Thr590, pan-Thr/Ser) and TBC1D4 (Ser588, Thr642, pan-Thr/Ser) phosphorylation. In cell-free assays, CaMKKα increased TBC1D1 (Thr590, pan-Thr/Ser) and TBC1D4 (Ser588, pan-Thr/Ser) phosphorylation. Collectively, these results demonstrate that caCaMKKα stimulates glucose uptake additively with insulin, and in insulin-resistant muscle, and alters the phosphorylation of TBC1D1/TBC1D4.
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影响因子：
64.8
作者：
Yano, S;Tokumitsu, H;Sodeling, TR
通讯作者：
Sodeling, TR
影响因子：
4.1
作者：
FERRE, P;LETURQUE, A;GIRARD, J
通讯作者：
GIRARD, J
影响因子：
4.8
作者：
Kramer, Henning F.;Witczak, Carol A.;Goodyear, Laurie J.
通讯作者：
Goodyear, Laurie J.
DOI：
10.1073/pnas.76.9.4350
发表时间：
1979-01-01
影响因子：
11.1
作者：
TOWBIN, H;STAEHELIN, T;GORDON, J
通讯作者：
GORDON, J
影响因子：
8.2
作者：
Jorgensen, S. Beck;O'Neill, H. M.;Steinberg, G. R.
通讯作者：
Steinberg, G. R.