Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle

Abstract

Muscle contraction causes an increase in activity of 5'-AMP-activated protein kinase (AMPK). This study was designed to determine whether chronic chemical activation of AMPK will increase mitochondrial enzymes, GLUT-4, and hexokinase in different types of skeletal muscle of resting rats. In acute studies, rats were subcutaneously injected with either 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 1 mg/g body wt) in 0.9% NaCl or with 0.9% NaCl alone and were then anesthetized for collection and freezing of tissues. AMPK activity increased in the superficial, white region of the quadriceps and in soleus muscles but not in the deep, red region of the quadriceps muscle. Acetyl-CoA carboxylase (ACC) activity, a target for AMPK, decreased in all three muscle types in response to AICAR injection but was lowest in the white quadriceps. In rats given daily, 1 mg/g body wt, subcutaneous injections of AICAR for 4 wk, activities of citrate synthase, succinate dehydrogenase, and malate dehydrogenase were increased in white quadriceps and soleus but not in red quadriceps. Cytochrome c and delta-aminolevulinic acid synthase levels were increased in white, but not red, quadriceps. Carnitine palmitoyl-transferase and hydroxy-acyl-CoA dehydrogenase were not significantly increased. Hexokinase was markedly increased in all three muscles, and GLUT-4 was increased in red and white quadriceps. These results suggest that chronic AMPK activation may mediate the effects of muscle contraction on some, but not all, biochemical adaptations of muscle to endurance exercise training.

Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats

“…This is an important finding, in view of the fact that long-term exposure to other AMPK activators, such as AICAR, produces a moderate increase in the liver weight of animals [35,36] that has been considered a potential side-effect of this kind of molecule, and which has not been observed in the chronic treatment with resveratrol.…”

AMP-activated protein kinase regulates the expression of monocarboxylate transporter 4 in skeletal muscle

“…Several studies have shown that 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an AMPK activator, activates glucose transport and increases the expression of glucose transporter 4 (GLUT4) and several metabolic enzymes in skeletal muscle (Buhl et al, 2001;Holmes et al, 1999Holmes et al, , 2005Ojuka et al, 2002;Stoppani et al, 2002;Winder et al, 2000;Zheng et al, 2001). It has been reported that an increase in glucose uptake induced by AICAR results in increased lactic acid production in isolated rat skeletal muscle (Miyamoto et al, 2007).…”

Leptinomimetic effects of the AMP kinase activator AICAR in leptin-resistant rats: prevention of diabetes and ectopic lipid deposition

“…Thus, by virtue of its actions on these enzymes, AMPK activation would both increase the oxidation of fatty acids and diminish their esterification to form triglycerides and other glycerolipids. Furthermore, increases in AMPK activity caused by administering the AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), are associated with anti-obesity [19,20] and insulin-sensitising effects [21,22,23] and genetically mediated increases in uncoupling proteins [24,25] in rodents.…”