CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle
CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle
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DOI：
10.1152/ajpendo.00659.2009
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发表时间：
2010-06-01
影响因子：
5.1
通讯作者：
Goodyear, Laurie J.
中科院分区：
文献类型：
--
作者：
Witczak, Carol A.;Jessen, Niels;Goodyear, Laurie J.
维察克CA， Jessen N, Warro DM, Toyoda T, Fujii N, Anderson ME, Hirshman MF, Goodyear LJ。CaMKII调节小鼠骨骼肌收缩，但不调节胰岛素诱导的葡萄糖摄取。[J] .中国生物医学工程学报，2016,31(2):559 - 563。首次发表于2010年3月9日；doi: 10.1152 / ajpendo.00659.2009。-使用化学抑制剂的研究表明，Ca2+敏感丝氨酸/苏氨酸激酶Ca2+/钙调素依赖性蛋白激酶II （CaMKII）是骨骼肌胰岛素和收缩刺激的葡萄糖摄取的关键调节剂。然而，由于这些抑制剂的非特异性，CaMKII在调节葡萄糖摄取中可能发挥的具体作用尚不清楚。我们试图确定CaMKII的特异性抑制是否会损害胰岛素和/或收缩诱导的小鼠骨骼肌葡萄糖摄取。将含有CaMKII抑制肽（KKALHRQEAVDCL）或对照肽（KKALHAQERVDCL）的绿色荧光蛋白表达载体通过体内电穿孔转染胫骨前肌。1周后，评估肌肉的肽表达、CaMK活性、胰岛素和收缩诱导的2-[H-3]脱氧葡萄糖摄取、糖原浓度和细胞内信号蛋白的变化。与对照肽相比，CaMKII抑制肽的表达使肌肉CaMK活性降低了35%。胰岛素诱导的葡萄糖摄取在表达抑制肽的肌肉中没有改变。相反，抑制肽的表达显著降低了收缩诱导的肌肉葡萄糖摄取（类似于30%）。抑制肽不改变收缩引起的肌糖原减少。CaMKII抑制肽不会改变葡萄糖转运蛋白GLUT4的表达，也不会损害收缩诱导的amp活化蛋白激酶（Thr(172)）或TBC1D1/TBC1D4在磷酸化akt底物位点磷酸化的增加。这些结果表明CaMKII不调节胰岛素刺激下骨骼肌的葡萄糖摄取。然而，CaMKII在小鼠骨骼肌收缩诱导的葡萄糖摄取调节中起关键作用。
Witczak CA, Jessen N, Warro DM, Toyoda T, Fujii N, Anderson ME, Hirshman MF, Goodyear LJ. CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle. Am J Physiol Endocrinol Metab 298: E1150-E1160, 2010. First published March 9, 2010; doi:10.1152/ajpendo.00659.2009.-Studies using chemical inhibitors have suggested that the Ca2+-sensitive serine/threonine kinase Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of both insulin-and contraction-stimulated glucose uptake in skeletal muscle. However, due to nonspecificity of these inhibitors, the specific role that CaMKII may play in the regulation of glucose uptake is not known. We sought to determine whether specific inhibition of CaMKII impairs insulin- and/or contraction- induced glucose uptake in mouse skeletal muscle. Expression vectors containing green fluorescent protein conjugated to a CaMKII inhibitory (KKALHRQEAVDCL) or control (KKALHAQERVDCL) peptide were transfected into tibialis anterior muscles by in vivo electroporation. After 1 wk, muscles were assessed for peptide expression, CaMK activity, insulin-and contraction-induced 2-[H-3]deoxyglucose uptake, glycogen concentrations, and changes in intracellular signaling proteins. Expression of the CaMKII inhibitory peptide decreased muscle CaMK activity similar to 35% compared with control peptide. Insulin-induced glucose uptake was not changed in muscles expressing the inhibitory peptide. In contrast, expression of the inhibitory peptide significantly decreased contraction-induced muscle glucose uptake (similar to 30%). Contraction-induced decreases in muscle glycogen were not altered by the inhibitory peptide. The CaMKII inhibitory peptide did not alter expression of the glucose transporter GLUT4 and did not impair contraction-induced increases in the phosphorylation of AMP-activated protein kinase (Thr(172)) or TBC1D1/TBC1D4 on phospho-Akt substrate sites. These results demonstrate that CaMKII does not regulate insulin-stimulated glucose uptake in skeletal muscle. However, CaMKII plays a critical role in the regulation of contraction-induced glucose uptake in mouse skeletal muscle.