CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle

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-[3H]deoxyglucose uptake, glycogen concentrations, and changes in intracellular signaling proteins. Expression of the CaMKII inhibitory peptide decreased muscle CaMK activity ∼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 (∼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 (Thr172) 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

Mechanical testing of bituminous mixtures : Chapter 4. In : Advances in interlaboratory testing and evaluation of bituminous materials, RILEM State of the Art Reports 9

This chapter focuses on permanent deformation, which is at the origin of pavement rutting. Fiirst experimental laboratory tools and associated analyses related to permanent deformations are presented