Distinct Signals Regulate AS160 Phosphorylation in Response to Insulin, AICAR, and Contraction in Mouse Skeletal Muscle

• DOI: 10.2337/db06-0150
• Publication Date: 2006-06-27T18:39:44Z
• Authors: Henning F. Kramer; Carol A. Witczak; Nobuharu Fujii; Niels Jessen; Eric B. Taylor; David E. Arnolds; Kei Sakamoto; Michael F. Hirshman; Laurie J. Goodyear
• Keywords: AMPK; EDL; Male; 0301 basic medicine; α2i; aPKC; Mice; 03 medical and health sciences; Animals; Insulin; Phosphorylation; Muscle, Skeletal; extensor digitorum longus; GTPase-activating protein; Glucose Transporter Type 4; AMP-activated protein kinase; Adenylate Kinase; GTPase-Activating Proteins; α2-inactive; GAP; Ribonucleotides; Aminoimidazole Carboxamide; Akt substrate of 160 kDa; phospho-Akt substrate; Mice, Inbred C57BL; Kinetics; Protein Transport; atypical protein kinase C; AS160; Female; PAS; Muscle Contraction; Signal Transduction

Insulin and contraction increase GLUT4 translocation in skeletal muscle via distinct signaling mechanisms. Akt substrate of 160 kDa (AS160) mediates insulin-stimulated L6 myotubes, presumably through activation Akt. Using vivo, vitro, situ methods, insulin, contraction, the AMP-activated protein kinase (AMPK) activator AICAR all increased AS160 phosphorylation mouse muscle. Insulin-stimulated was fully blunted by wortmannin vitro Akt2 knockout (KO) mice vivo. In contrast, contraction-stimulated only partially decreased unaffected KO mice, suggesting additional regulatory To determine if AMPK signaling, we used α2-inactive (α2i) transgenic mice. AICAR-stimulated inhibited, whereas reduced α2i Combined α2 inhibition treatment did not ablate phosphorylation. Maximal together with either or an additive manner. conclusion, may be a point convergence linking signaling. While activities are essential for insulin AICAR, respectively, neither is indispensable entire effects on