Metabolomics:Open Access

ISSN: 2153-0769

Open Access

Involvement of Amp Kinase in Glucose Uptake and Palmitate Oxidation in L6 Muscle Cell Cultures


Ouyang J and Ochs RS

AICAR (5-aminoimidazole-4-carboxamide 1-ß-D-ribonucleoside) is known to activate the AMP-activated protein kinase (AMPK) in many cell types, including skeletal muscle. We showed that AICAR activated glucose uptake, fatty acid oxidation, and lactate formation by L6 skeletal muscle cell cultures. All of the actions were duplicated by adiponectin, another known activator of AMPK, demonstrating selectivity of AICAR. Moreover, AICAR and adiponectin similarly caused phosphorylation of AMPK, and its target proteins acetyl CoA carboxylase and S6Kinase. While creatine treatment of cells is known to greatly enhance creatine and creatine phosphate levels, it was proposed to paradoxically activate AMPK, and yet not affect glucose transport. However, we found creatine treatment to be without effect on glucose transport, fatty acid oxidation, or phosphorylation of AMPK or its target proteins. Unlike AICAR and adiponectin, creatine treatment stimulated glycogen formation from glucose and inhibited lactate formation. Consistent with this, we observed a diminution in phosphofructokinase expression. Thus, we conclude that creatine and creatine phosphate are not significant allosteric modulators of AMPK in intact cells. We investigated the role of AMPK in glycogen metabolism, using an inhibitor of glycogen phosphorylase. While the inhibitor enhanced glucose incorporation into glycogen, AICAR and adiponectin still diminished glycogen formation, supporting a direct action of AMPK on glycogen synthase. To probe the mechanism for adiponectin, we used siRNA constructs against adenyate kinase and LKB1 (the AMPK kinase). We concluded that adiponectin likely acts through an activation of LKB1, rather than indirectly increasing the turnover of ATP, involving adenylate kinase.


Share this article

Google Scholar citation report
Citations: 895

Metabolomics:Open Access received 895 citations as per Google Scholar report

Metabolomics:Open Access peer review process verified at publons

Indexed In

arrow_upward arrow_upward