AMP-activated protein kinase regulation and action in skeletal muscle during exercise

2003 ◽  
Vol 31 (1) ◽  
pp. 191-195 ◽  
Author(s):  
N. Musi ◽  
H. Yu ◽  
L.J. Goodyear
Keyword(s):  
Protein Kinase ◽  
Exercise Training ◽  
Metabolic Pathways ◽  
Acute Exercise ◽  
Glycogen Content ◽  
Glycogen Metabolism ◽  
Acid Oxidation ◽  
Ampk Activity ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase

Physical exercise increases muscle glucose uptake, enhances insulin sensitivity and leads to fatty acid oxidation in muscle. The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is strongly activated during muscle contraction due to acute decreases in ATP/AMP and phosphocreatine/creatine ratios. Accumulating evidence suggests that AMPK plays an important role in mediating these metabolic processes. Furthermore, AMPK has been implicated in regulating gene transcription and therefore may play a role in some of the cellular adaptations to training exercise. There is also evidence that changes in AMPK activity result in altered cellular glycogen content, suggesting that this enzyme regulates glycogen metabolism. Recent studies have shown that the magnitude of AMPK activation and associated metabolic responses are affected by factors such as glycogen content, exercise training and fibre type. In summary, AMPK regulates several metabolic pathways during acute exercise and modifies the expression of many genes involved in the adaptive changes to exercise training.

scholarly journals Regulation of glucose transport by the AMP-activated protein kinase

2004 ◽  
Vol 63 (2) ◽  
pp. 205-210 ◽  
Author(s):  
Nobuharu Fujii ◽  
William G. Aschenbach ◽  
Nicolas Musi ◽  
Michael F. Hirshman ◽  
Laurie J. Goodyear
Keyword(s):  
Protein Kinase ◽  
Glucose Transport ◽  
Glycogen Content ◽  
Acid Oxidation ◽  
Ampk Activation ◽  
Muscle Biology ◽  
Ampk Activity ◽  
Energy Sensing ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated during exercise and muscle contraction as a result of acute decreases in ATP:AMP and phosphocreatine:creatine. Physical exercise increases muscle glucose uptake, enhances insulin sensitivity and leads to fatty acid oxidation in muscle. An important issue in muscle biology is to understand whether AMPK plays a role in mediating these metabolic processes. AMPK has also been implicated in regulating gene transcription and, therefore, may function in some of the cellular adaptations to training exercise. Recent studies have shown that the magnitude of AMPK activation and associated metabolic responses are affected by factors such as glycogen content, exercise training and fibre type. There have also been conflicting reports as to whether AMPK activity is necessary for contraction-stimulated glucose transport. Thus, during the next several years considerably more research will be necessary in order to fully understand the role of AMPK in regulating glucose transport in skeletal muscle.

Abstract 88: AMP-activated Protein Kinase Signaling Mediates the Cardioprotective effect of Antithrombin against Myocardial Ischemia and Reperfusion Injury

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ji Li ◽  
Yina Ma ◽  
Jinli Wang ◽  
Hui Yang ◽  
Yanqing Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Myocardial Ischemia ◽  
Coagulation System ◽  
Acid Oxidation ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion ◽  
Substrate Metabolism ◽  
High Affinity ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

Background: Antithrombin (AT) is an endogenous protein of the serpin superfamily involved in regulation of the proteolytic activity of the serine proteases of the coagulation system. AT is known to exhibit anti-inflammatory and cardioprotective properties when it binds to distinct heparan sulfate proteoglycans (HSPGs) on vascular endothelial cells. The energy sensor AMP-activated protein kinase (AMPK) plays an important cardioprotective role during myocardial ischemia and reperfusion (I/R). The objective of this study was to investigate whether the cardioprotective signaling function of AT against I/R injury is mediated through the AMPK pathway. Methods and Results: The cardioprotective activities of wild-type (WT) AT and its two recombinant derivatives, one having high affinity and the other no affinity for heparin, were evaluated in an acute I/R (20 min/4 h) injury model in which the left anterior descending coronary artery (LAD) was occluded. The serpin derivatives were given 5 min before reperfusion. The results showed that AT-WT can activate the protective AMPK signaling pathway in both in vivo and ex vivo conditions. Blocking AMPK activity abolished the cardioprotective function of AT against I/R injury. The AT derivative having high affinity for heparin was more effective in activating AMPK, but the derivative lacking any affinity for heparin was inactive in eliciting AMPK-dependent cardioprotective activity. The activation of AMPK by AT inhibited the inflammatory c-Jun N-terminal protein kinase (JNK) pathway during I/R. Further studies revealed that the AMPK activity of AT also modulates cardiac substrate metabolism by increasing glucose oxidation but inhibiting fatty acid oxidation during I/R. Conclusions: These results suggest that AT binds to vascular HSPGs to invoke a cardioprotective function by triggering cardiac AMPK activation, thereby attenuating JNK inflammatory signaling pathways and modulating substrate metabolism during I/R.

scholarly journals Role of Hypothalamic Adenosine 5′-Monophosphate-Activated Protein Kinase in the Impaired Counterregulatory Response Induced by Repetitive Neuroglucopenia

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1367-1375 ◽  
Author(s):  
Thierry Alquier ◽  
Junji Kawashima ◽  
Youki Tsuji ◽  
Barbara B. Kahn
Keyword(s):  
Protein Kinase ◽  
Glycogen Content ◽  
Glucose Sensor ◽  
Critical Role ◽  
Glucose Sensing ◽  
Dorsomedial Hypothalamus ◽  
Hormone Responses ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

Antecedent hypoglycemia blunts counterregulatory responses that normally restore glycemia, a phenomenon known as hypoglycemia-associated autonomic failure (HAAF). The mechanisms leading to impaired counterregulatory responses are largely unknown. Hypothalamic AMP-activated protein kinase (AMPK) acts as a glucose sensor. To determine whether failure to activate AMPK could be involved in the etiology of HAAF, we developed a model of HAAF using repetitive intracerebroventricular (icv) injection of 2-deoxy-d-glucose (2DG) resulting in transient neuroglucopenia in normal rats. Ten minutes after a single icv injection of 2DG, both α1- and α2-AMPK activities were increased 30–50% in arcuate and ventromedial/dorsomedial hypothalamus but not in other hypothalamic regions, hindbrain, or cortex. Increased AMPK activity persisted in arcuate hypothalamus at 60 min after 2DG injection when serum glucagon and corticosterone levels were increased 2.5- to 3.4-fold. When 2DG was injected icv daily for 4 d, hypothalamic α1- and α2-AMPK responses were markedly blunted in arcuate hypothalamus, and α1-AMPK was also blunted in mediobasal hypothalamus 10 min after 2DG on d 4. Both AMPK isoforms were activated normally in arcuate hypothalamus at 60 min. Counterregulatory hormone responses were impaired by recurrent neuroglucopenia and were partially restored by icv injection of 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside, an AMPK activator, before 2DG. Glycogen content increased 2-fold in hypothalamus after recurrent neuroglucopenia, suggesting that glycogen supercompensation could be involved in down-regulating the AMPK glucose-sensing pathway in HAAF. Thus, activation of hypothalamic AMPK may be important for the full counterregulatory hormone response to neuroglucopenia. Furthermore, impaired or delayed AMPK activation in specific hypothalamic regions may play a critical role in the etiology of HAAF.

AMP-activated protein kinase regulates gene expression by direct phosphorylation of nuclear proteins

2003 ◽  
Vol 31 (1) ◽  
pp. 224-227 ◽  
Author(s):  
T. Leff
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Protein Kinase ◽  
Gene Transcription ◽  
Metabolic Pathways ◽  
Energy Charge ◽  
Nuclear Proteins ◽  
Cellular Energy ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

One of the primary functions of AMP-activated protein kinase (AMPK) is to regulate the metabolic pathways in response to reduced cellular energy charge. Most of the known targets of the kinase are cytoplasmic enzymes involved in both catabolic and anabolic metabolism. In addition, activation of AMPK in many cells results in changes in the pattern of gene expression. Although some of these effects are undoubtedly secondary responses to modified cellular metabolism, it is possible that in addition to its well-characterized function in the cytoplasm, AMPK also directly phosphorylates and regulates proteins involved in gene transcription. There are now several examples of transcription factors, cofactors and components of the transcriptional core machinery that are directly phosphorylated and regulated by AMPK. Here I review these examples and discuss the significance of AMPK activity in the nucleus.

5′-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle

2004 ◽  
Vol 286 (3) ◽  
pp. E411-E417 ◽  
Author(s):  
Christian Frøsig ◽  
Sebastian B. Jørgensen ◽  
D. Grahame Hardie ◽  
Erik A. Richter ◽  
Jørgen F. P. Wojtaszewski
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Exercise Training ◽  
Protein Content ◽  
Endurance Training ◽  
Human Skeletal Muscle ◽  
Protein Kinase Activity ◽  
Local Contraction ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The 5′-AMP-activated protein kinase (AMPK) is proposed to be involved in signaling pathways leading to adaptations in skeletal muscle in response to both a single exercise bout and exercise training. This study investigated the effect of endurance training on protein content of catalytic (α1, α2) and regulatory (β1, β2 and γ1, γ2, γ3) subunit isoforms of AMPK as well as on basal AMPK activity in human skeletal muscle. Eight healthy young men performed supervised one-legged knee extensor endurance training for 3 wk. Muscle biopsies were obtained before and 15 h after training in both legs. In response to training the protein content of α1, β2 and γ1 increased in the trained leg by 41, 34, and 26%, respectively (α1 and β2 P < 0.005, γ1 P < 0.05). In contrast, the protein content of the regulatory γ3-isoform decreased by 62% in the trained leg ( P = 0.01), whereas no effect of training was seen for α2, β1, and γ2. AMPK activity associated with the α1- and the α2-isoforms increased in the trained leg by 94 and 49%, respectively (both P < 0.005). In agreement with these observations, phosphorylation of α-AMPK-(Thr172) and of the AMPK target acetyl-CoA carboxylase-β(Ser221) increased by 74 and 180%, respectively (both P < 0.001). Essentially similar results were obtained in four additional subjects studied 55 h after training. This study demonstrates that protein content and basal AMPK activity in human skeletal muscle are highly susceptible to endurance exercise training. Except for the increase in γ1 protein, all observed adaptations to training could be ascribed to local contraction-induced mechanisms, since they did not occur in the contralateral untrained muscle.

Suppression of 5′-AMP-activated protein kinase activity does not impair recovery of contractile function during reperfusion of ischemic hearts

2009 ◽  
Vol 297 (1) ◽  
pp. H313-H321 ◽  
Author(s):  
Clifford D. L. Folmes ◽  
Cory S. Wagg ◽  
Mei Shen ◽  
Alexander S. Clanachan ◽  
Rong Tian ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Fatty Acid Oxidation ◽  
Functional Recovery ◽  
Recovery Of Function ◽  
High Energy ◽  
Acid Oxidation ◽  
Protein Kinase Activity ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

Activation of 5′-AMP-activated protein kinase (AMPK) may benefit the heart during ischemia-reperfusion by increasing energy production. While AMPK stimulates glycolysis, mitochondrial oxidative metabolism is the major source of ATP production during reperfusion of ischemic hearts. Stimulating AMPK increases mitochondrial fatty acid oxidation, but this is usually accompanied by a decrease in glucose oxidation, which can impair the functional recovery of ischemic hearts. To examine the relationship between AMPK and cardiac energy substrate metabolism, we subjected isolated working mouse hearts expressing a dominant negative (DN) α2-subunit of AMPK (AMPK-α2 DN) to 20 min of global no-flow ischemia and 40 min of reperfusion with Krebs-Henseleit solution containing 5 mM [U-14C]glucose, 0.4 mM [9, 10-3H]palmitate, and 100 μU/ml insulin. AMPK-α2 DN hearts had reduced AMPK activity at the end of reperfusion (82 ± 9 vs. 141 ± 7 pmol·mg−1·min−1) with no changes in high-energy phosphates. Despite this, AMPK-α2 DN hearts had improved recovery of function during reperfusion (14.9 ± 0.8 vs. 9.4 ± 1.4 beats·min−1·mmHg·10−3). During reperfusion, fatty acid oxidation provided 44.0 ± 2.8% of total acetyl-CoA in AMPK-α2 DN hearts compared with 55.0 ± 3.2% in control hearts. Since insulin can inhibit both AMPK activation and fatty acid oxidation, we also examined functional recovery in the absence of insulin. Functional recovery was similar in both groups despite a decrease in AMPK activity and a decreased reliance on fatty acid oxidation during reperfusion (66.4 ± 9.4% vs. 85.3 ± 4.3%). These data demonstrate that the suppression of cardiac AMPK activity does not produce an energetically compromised phenotype and does not impair, but may in fact improve, the recovery of function after ischemia.

Additive effect of contraction and insulin on glucose uptake and glycogen synthase in muscle with different glycogen contents

2010 ◽  
Vol 108 (5) ◽  
pp. 1106-1115 ◽  
Author(s):  
Yu-Chiang Lai ◽  
Elham Zarrinpashneh ◽  
Jørgen Jensen
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Skeletal Muscles ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Additive Effect ◽  
Insulin Stimulation ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Pkb Phosphorylation

Insulin and contraction regulate glucose uptake and glycogen synthase (GS) via distinct mechanisms in skeletal muscles, and an additive effect has been reported. Glycogen content is known to influence both contraction- and insulin-stimulated glucose uptake and GS activity. Our study reports that contraction and insulin additively stimulate glucose uptake in rat epitrochlearis muscles with normal (NG) and high (HG) glycogen contents, but the additive effect was only partial. In muscles with low glycogen (LG) content no additive effect was seen, but glucose uptake was higher in LG than in NG and HG during contraction, insulin stimulation, and when the two stimuli were combined. In LG, contraction-stimulated AMP-activated protein kinase (AMPK) activity and insulin-stimulated PKB phosphorylation were higher than in NG and HG, but phosphorylation of Akt substrate of 160 kDa was not elevated correspondingly. GLUT4 content was 50% increased in LG (rats fasted 24 h), which may explain the increased glucose uptake. Contraction and insulin also additively increased GS fractional activity in NG and HG but not in LG. GS fractional activity correlated most strongly with GS Ser641 phosphorylation ( R −0.94, P < 0.001). GS fractional activity also correlated with GS Ser7,10 phosphorylation, but insulin did not reduce GS Ser7,10 phosphorylation. In conclusion, an additive effect of contraction and insulin on glucose uptake and GS activity occurs in muscles with normal and high glycogen content but not in muscles with low glycogen content. Furthermore, contraction, insulin, and glycogen content all regulate GS Ser641 phosphorylation and GS fractional activity in concert.

scholarly journals Activation of AMPK Promotes Maturation of Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Liang Ye ◽  
Xinyuan Zhang ◽  
Qin Zhou ◽  
Bin Tan ◽  
Hao Xu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Acid Oxidation ◽  
Mitochondrial Structure ◽  
Myocardial Structure ◽  
Energy Sensing ◽  
Induced Pluripotent ◽  
And Function ◽  
Amp Activated Protein Kinase

Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) (hiPSC-CMs) are a promising cell source for disease modeling, myocardial regeneration, and drug assessment. However, hiPSC-CMs have certain immature fetal CM-like properties that are different from the characteristics of adult CMs in several aspects, including cellular structure, mitochondrial function, and metabolism, thus limiting their applications. Adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK) is an energy-sensing protein kinase involved in the regulation of fatty acid oxidation and mitochondrial biogenesis in cardiomyocytes. This study investigated the effects of AMPK on the maturation of hiPSC-CMs. Activation of AMPK in hiPSC-CMs significantly increased the expression of CM-specific markers and resulted in a more mature myocardial structure compared to that in the control cells. We found that activation of AMPK improved mitochondrial oxidative phosphorylation (OxPhos) and the oxygen consumption rate (OCR). Additionally, our data demonstrated that activation of AMPK increased mitochondrial fusion to promote the maturation of mitochondrial structure and function. Overall, activation of AMPK is an effective approach to promote hiPSC-CMs maturation, which may enhance the utility of hiPSC-CMs in clinical applications.

5′-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle

2003 ◽  
Vol 94 (2) ◽  
pp. 631-641 ◽  
Author(s):  
Jakob N. Nielsen ◽  
Kirsty J. W. Mustard ◽  
Drew A. Graham ◽  
Haiyan Yu ◽  
Christopher S. MacDonald ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Protein Kinase Activity ◽  
Trained Subjects ◽  
Protein Levels ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase ◽  
Sedentary Subjects

5′-AMP-activated protein kinase (AMPK) has been proposed to be a pivotal factor in cellular responses to both acute exercise and exercise training. To investigate whether protein levels and gene expression of catalytic (α1, α2) and regulatory (β1, β2, γ1, γ2, γ3) AMPK subunits and exercise-induced AMPK activity are influenced by exercise training status, muscle biopsies were obtained from seven endurance exercise-trained and seven sedentary young healthy men. The α1- and α2-AMPK mRNA contents in trained subjects were both 117 ± 2% of that in sedentary subjects (not significant), whereas mRNA for γ3 was 61 ± 1% of that in sedentary subjects (not significant). The level of α1-AMPK protein in trained subjects was 185 ± 34% of that in sedentary subjects ( P < 0.05), whereas the levels of the remaining subunits (α2, β1, β2, γ1, γ2, γ3) were similar in trained and sedentary subjects. At the end of 20 min of cycle exercise at 80% of peak O2 uptake, the increase in phosphorylation of α-AMPK (Thr172) was blunted in the trained group (138 ± 38% above rest) compared with the sedentary group (353 ± 63% above rest) ( P < 0.05). Acetyl CoA-carboxylase β-phosphorylation (Ser221), which is a marker for in vivo AMPK activity, was increased by exercise in both groups but to a lower level in trained subjects (32 ± 5 arbitrary units) than in sedentary controls (45 ± 1 arbitrary units) ( P < 0.01). In conclusion, trained human skeletal muscle has increased α1-AMPK protein levels and blunted AMPK activation during exercise.

AMP-activated protein kinase and the metabolic syndrome

2005 ◽  
Vol 33 (2) ◽  
pp. 362-366 ◽  
Author(s):  
L.G.D. Fryer ◽  
D. Carling
Keyword(s):  
Protein Kinase ◽  
Glycogen Metabolism ◽  
Energy Utilization ◽  
Whole Body ◽  
Acid Oxidation ◽  
Type Ii ◽  
Glucose Levels ◽  
The Metabolic Syndrome ◽  
Amp Activated Protein Kinase ◽  
Body Energy

The occurrence of Type II (non-insulin-dependent) diabetes and obesity and their associated morbidities continue to increase and they are rapidly reaching epidemic proportions. AMPK (AMP-activated protein kinase) was initially thought of as an intracellular ‘fuel gauge’ responding to a decrease in the level of ATP by increasing energy production and decreasing energy utilization. Recent studies have shown that AMPK plays a role in controlling the whole body energy homoeostasis, including the regulation of plasma glucose levels, fatty acid oxidation and glycogen metabolism. In addition to its effects on the periphery, AMPK has been found to play a key role in the control of food intake through its regulation by hormones, including leptin, within the hypothalamus. The control of AMPK activity, therefore, provides an attractive target for therapeutic intervention in metabolic disorders such as obesity and Type II diabetes. Indeed, a number of physiological and pharmacological factors that are beneficial in these disorders have been shown to act, at least in part, through the activation of AMPK.

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