Differential attenuation of AMPK activation during acute exercise following exercise training or AICAR treatment

McConell, Glenn K.; Manimmanakorn, Apiwan; Lee, Robert S.; Kemp, Bruce E.; Linden, Kelly; Wadley, Glenn D.

doi:10.1152/japplphysiol.01371.2007

Cited by 19 publications

(18 citation statements)

References 36 publications

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“…The increase of phosphorylated acetyl-CoA carboxylase (pACC) is consistent with the activation of AMPK under exercise (Fig. 1A) [5,11]. However, the effect of AICAR on blood glucose levels was greatly diminished in sk-NSPL1-deficient mice (Fig.…”

Section: Resultssupporting

confidence: 68%

“…First, whole skeletal muscle samples were freeze-dried and solubilized with 1% Triton X-100 in accordance with previous reports [11]. Second, F2 membrane fractions [3], which are abundant in sk-NSPL1 and GLUT4 as described previously [9], were prepared from the hindlimbs of mice after electrical stimulation, insulin injection, or AICAR administration.…”

Section: Methodsmentioning

confidence: 99%

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Involvement of a Phosphorylation-Mediated Pathway to Regulate the Function of NSPL1 in Exercise

Ikemoto¹,

Suzuki²,

Onoe³

2011

The Journal of Veterinary Medical Science

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ABSTRACT. Skeletal-type neuroendocrine-specific protein like 1 (sk-NSPL1) has been demonstrated to be physiologically important in regulating the membrane translocation of glucose transporter 4 (GLUT4) in skeletal muscles. We investigated the levels of phosphorylation in proteins that are thought to be involved in exercise in wild-type and sk-NSPL1-deficient muscles with specific antibodies and phosphate-metal affinity chromatography resin (p-resin). In both normal skeletal muscle and sk-NSPL1-deficient muscle, adenosine monophosphate (AMP)-dependent kinase (AMPK) and acetyl-CoA carboxylase (ACC) were phosphorylated and adsorbed onto p-resin at high levels after exercise. On the other hand, the effect of 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR), which is an activator of AMPK, in blood glucose was greatly diminished in mutant mice. P-resin adsorbed sk-NSPL1 in the membrane fraction from wildtype muscle after exercise and AICAR administration. Isolated sk-NSPL1 from wild-type also had increased adsorption onto p-resin after treatment with Ca 2+ and adenosine triphosphate (ATP). After long-term incubation of sk-NSPL1-containing membrane without ATP, sk-NSPL1 adsorption onto anion-exchange resin was drastically reduced. These results suggest that the function of sk-NSPL1 is regulated by a [Ca 2+ ] i -and AMPK-mediated pathway under exercise, and support the hypothesis that sk-NSPL1 is an important factor in the downstream of the exercise-dependent pathway in GLUT4 translocation.KEY WORDS: exercise, GLUT4 translocation, insulin, phosphorylation, skeletal muscle.J. Vet. Med. Sci. 73(6): 733-738, 2011 Glucose uptake in skeletal muscles, which is regulated by membrane translocation of glucose transporter 4 (GLUT4) from internal stores to the cell membrane, can change blood glucose levels in the whole body [7,14]. Therefore, resolving the molecular mechanisms that underlie this function is important. We previously reported that skeletal-type neuroendocrine-specific protein-like 1 (sk-NSPL1) plays an important role in GLUT4 translocation induced by contraction/exercise in skeletal muscles [9]. However, the precise mechanism by which sk-NSPL1 works has not been elucidated.In the present study, we examined the level of phosphorylation of adenosine monophosphate (AMP)-dependent kinase (AMPK) in sk-NSPL1-deficient muscle, which is affected by changes in AMP/adenosine triphosphate (ATP) in cells under muscle contraction, and the effect of 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR) on blood glucose, which can activate AMPK [12,17]. Our results suggest that sk-NSPL1 might be involved downstream of the AMPK-mediated pathway in GLUT4 translocation. We also investigated whether isolated sk-NSPL1 adsorbed on to phosphate-metal affinity chromatography resin (p-resin) in response to contraction or by elevation of [Ca 2+ ] i within physiological levels. Our data suggest that a phosphorylation-mediated change in function of sk-NSPL1 may be involved in the regulation of exercise-induced GLUT4 transloca...

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Section: Resultssupporting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Involvement of a Phosphorylation-Mediated Pathway to Regulate the Function of NSPL1 in Exercise

Ikemoto¹,

Suzuki²,

Onoe³

2011

The Journal of Veterinary Medical Science

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“…However, 10 d of AICAR treatment mimicked the effect of 10 d of training on skeletal muscle AMPK activation (McConell et al 2008). In addition, 6 d of GW501516 or AICAR treatment significantly changed muscle metabolic gene expression (Narkar et al 2008).…”

mentioning

confidence: 99%

Endurance factors improve hippocampal neurogenesis and spatial memory in mice

Kobilo¹,

Yuan²,

Praag³

2011

Learn. Mem.

102

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Physical activity improves learning and hippocampal neurogenesis. It is unknown whether compounds that increase endurance in muscle also enhance cognition. We investigated the effects of endurance factors, peroxisome proliferator-activated receptor d agonist GW501516 and AICAR, activator of AMP-activated protein kinase on memory and neurogenesis. Mice were injected with GW for 7 d or AICAR for 7 or 14 d. Two weeks thereafter mice were tested in the Morris water maze. AICAR (7 d) and GW improved spatial memory. Moreover, AICAR significantly, and GW modestly, elevated dentate gyrus neurogenesis. Thus, pharmacological activation of skeletal muscle may mediate cognitive effects.Physical activity has many benefits for brain function ranging from memory to mood (Hillman et al. 2008). There is a strong positive correlation between running and performance in hippocampus-dependent spatial memory tasks (van Praag 2008). Research into mechanisms underlying effects of running on the brain has mainly focused on changes in neurotransmitters, neurotrophins, spine density, and hippocampal neurogenesis (Cotman et al. 2007;Gomez-Pinilla et al. 2008;Hillman et al. 2008;van Praag 2008). Conversely, the peripheral triggers of the cellular and molecular cascades in the brain that lead to improved cognition have remained unclear. It has been suggested that serum insulin-like growth factor-1 (IGF) may play a role as the peripheral blockade abolished the running-induced enhancement of hippocampal neurogenesis (Trejo et al. 2001). Similar observations were made following systemic blockade of vascular endothelial growth factor (VEGF) (Fabel et al. 2003). However, the possibility that skeletal muscle activation as a result of exercise or pharmacological agents underlies cognitive effects of aerobic activity has not been explored.Recently, transcriptional factors regulating muscle fiber contractile and metabolic genes have been identified (Wang et al. 2004). The peroxisome proliferator activated receptor d (PPARd) is a transcription factor that regulates fast-twitch muscle fiber contraction and metabolism. Overexpression of this factor increased oxidative muscle fiber number. In addition, administration of the selective agonist GW501516 increased exercise stamina when combined with training (Narkar et al. 2008). PPARd is controlled by the AMP-activated protein kinase (AMPK), a master metabolic regulator important for glucose homeostasis, appetite, and exercise physiology (Hardie 2004). Treatment with AMPK agonist AICAR enhanced running endurance by 45% in sedentary mice (Narkar et al. 2008). It has not been determined whether the effects of these compounds extend from the periphery to brain function, and may influence hippocampal neurogenesis and spatial memory. Here we show that systemic pretreatment with AICAR, and more modestly, GW501516, 2 wk prior to behavioral testing enhances spatial learning and hippocampal neurogenesis.In the present study, female C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME) 2-mo-old, were housed under standa...

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“…Before training (*pretest) the 2 h constant-load exercise bout (171 ± 4 W) markedly activated AMPK, as evidenced by increased AMPKa phosphorylation status. The 6-week training programme expectedly negated this exercise-induced activation of AMPK (McConell et al 2005(McConell et al , 2008Benziane et al 2008) (see Fig. 3a), which probably reflects facilitated energy homeostasis in muscle cells during a given absolute exercise intensity after a training period (Chesley et al 1996;McConell et al 2005).…”

Section: Pln (mentioning

confidence: 95%

“…For example, consistent exercise training upregulates AMPKa phosphorylation status in human muscle (Frosig et al 2004;Lee-Young et al 2009;Benziane et al 2008), whilst exercise-induced activation of AMPK is downregulated (McConell et al 2005;McConell et al 2008;Lee-Young et al 2009;Benziane et al 2008). Furthermore, after 6 weeks of aerobic training in mice, cardiomyocytes displayed elevated PLN 17 phosphorylation in conjunction with increased CaMKII phosphorylation at Thr 287 (Kemi et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Training in the fasted state facilitates re-activation of eEF2 activity during recovery from endurance exercise

2010

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Differential attenuation of AMPK activation during acute exercise following exercise training or AICAR treatment

Cited by 19 publications

References 36 publications

Involvement of a Phosphorylation-Mediated Pathway to Regulate the Function of NSPL1 in Exercise

Involvement of a Phosphorylation-Mediated Pathway to Regulate the Function of NSPL1 in Exercise

Endurance factors improve hippocampal neurogenesis and spatial memory in mice

Training in the fasted state facilitates re-activation of eEF2 activity during recovery from endurance exercise

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