α1 AMPK Activation is Required for Stimulation of Glucose Uptake by Twitch Contraction, but not by H2O2, in Mouse Skeletal Muscle
Abstract Number: 1042-P
Authors: THOMAS E. JENSEN, JØRGEN F. WOJTASZEWSKI, ERIK A. RICHTER, Copenhagen, Denmark
Institutions: Copenhagen, Denmark
Results: Activation of one of the two catalytic AMPK isoforms, α2 AMPK, the skeletal muscle enriched catalytic α2 AMPK isoform is necessary to increase non-insulin dependent glucose uptake into skeletal muscle with certain stimuli, including 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), hypoxia and metabolic uncoupling. This suggests that α2 AMPK is the major isoform eliciting increased glucose transport in muscle. Meanwhile, recent studies have observed correlations between catalytic α1 AMPK isoform activation and non-insulin dependent increase in glucose uptake in the absence of changes in α2 AMPK isoform activity, during low-intensity twitch-contraction and following H2O2 stimulation of skeletal muscle. However, the existence of a causal relationship remains to be investigated. This study directly evaluated the necessity of the α-AMPK catalytic subunits during these processes using AMPK transgenic mouse models. Following stimulation with H2O2 (3 mM, 20 min) or twitch-contraction (0.1 ms pulse, 2Hz, 2 min), signaling and 2-deoxyglucose uptake were measured in incubated soleus muscles from wildtype and muscle-specific kinase-dead AMPK (KD), α1 AMPK knokout or α2 AMPK knockout mice. H2O2 increased the activity of both α1 and α2 AMPK in addition to Akt phosphorylation, and H2O2-stimulated glucose uptake was not reduced in any of the AMPK transgenic mouse models compared with wild type. In contrast, twitch-contraction increased the activity of α1 AMPK, but not α2 AMPK activity nor Akt or AS160 phosphorylation. Glucose uptake was markedly lower in α1 AMPK knockout and KD AMPK muscles, but not in α2 AMPK knockout muscles, following twitch stimulation. These results provide strong genetic evidence that α1 AMPK, but not α2 AMPK, Akt or AS160, is required for twitch-contraction stimulated glucose uptake. This advances our understanding of the respective roles of α1 and α2 AMPK to regulation of glucose uptake, and suggests a previously overlooked role of α1 AMPK in this process. In contrast, AMPK is not essential for H2O2-stimulated muscle glucose uptake, as proposed by recent studies.
Category: Exercise - Animal