AMPK Activation of Flavonoids from Psidium guajava Leaves in L6 Rat Myoblast Cells and L02 Human Hepatic Cells

Objective. To isolate the hypoglycemic bioactive components from leaves of Psidium guajava and evaluate their AMP-activated protein kinase (AMPK) activities. Methods. A variety of column chromatography was used for the isolation of compounds, and nuclear magnetic resonance (NMR) and mass spectrum (MS) were used for the structure identification of compounds. AMP-activated protein kinase (AMPK) activity of compounds obtained from leaves of Psidium guajava was evaluated in L6 rat myoblast cells and L02 human hepatic cells by western blot. Results. Six principal flavonoids largely present in the leaves of Psidium guajava, quercetin (1), quercetin-3-O-α-L-arabinofuranoside (2), quercetin-3-O-α-L-arabinopyranoside (3), quercetin-3-O-β-D-galactopyranoside (4), quercetin-3-O-β-D-glucopyranoside (5), and quercetin-3-O-β-D-xylopyranoside (6), were obtained and compound 1–6 exhibited significant activity on AMPK activation both in L6 cells and L02 cells (p<0.01) compared with Control. In particular, the effects of quercetin on AMPK activation were extremely significant compared with Control (p<0.001). Conclusions. These findings demonstrated that these flavonoids had potential for the activation of AMPK and hypoglycemic activity.

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AMPK activation with AICAR provokes an acute fall in plasma [K+]

AJP Cell Physiology ◽

10.1152/ajpcell.00464.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. C126-C135 ◽

Cited By ~ 21

Author(s):

Dan Zheng ◽

Anjana Perianayagam ◽

Donna H. Lee ◽

M. Douglas Brannan ◽

Li E. Yang ◽

...

Keyword(s):

Protein Kinase ◽

Infusion Rate ◽

Extracellular Fluid ◽

Ampk Activation ◽

Conscious Rats ◽

Significant Fall ◽

Ampk Phosphorylation ◽

Atp Levels ◽

Ampk Activity ◽

Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK), activated by an increase in intracellular AMP-to-ATP ratio, stimulates pathways that can restore ATP levels. We tested the hypothesis that AMPK activation influences extracellular fluid (ECF) K+ homeostasis. In conscious rats, AMPK was activated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) infusion: 38.4 mg/kg bolus then 4 mg·kg−1·min−1 infusion. Plasma [K+] and [glucose] both dropped at 1 h of AICAR infusion and [K+] dropped to 3.3 ± 0.04 mM by 3 h, linearly related to the increase in muscle AMPK phosphorylation. AICAR treatment did not increase urinary K+ excretion. AICAR lowered [K+] whether plasma [K+] was chronically elevated or lowered. The K+ infusion rate needed to maintain baseline plasma [K+] reached 15.7 ± 1.3 μmol K+·kg−1·min−1 between 120 and 180 min AICAR infusion. In mice expressing a dominant inhibitory form of AMPK in the muscle (Tg-KD1), baseline [K+] was not different from controls (4.2 ± 0.1 mM), but the fall in plasma [K+] in response to AICAR (0.25 g/kg) was blunted: [K+] fell to 3.6 ± 0.1 in controls and to 3.9 ± 0.1 mM in Tg-KD1, suggesting that ECF K+ redistributes, at least in part, to muscle ICF. In summary, these findings illustrate that activation of AMPK activity with AICAR provokes a significant fall in plasma [K+] and suggest a novel mechanism for redistributing K+ from ECF to ICF.

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Effect of acute activation of 5′-AMP-activated protein kinase on glycogen regulation in isolated rat skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.01034.2006 ◽

2007 ◽

Vol 102 (3) ◽

pp. 1007-1013 ◽

Cited By ~ 53

Author(s):

Licht Miyamoto ◽

Taro Toyoda ◽

Tatsuya Hayashi ◽

Shin Yonemitsu ◽

Masako Nakano ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Muscle Glycogen ◽

Glycogen Synthase ◽

Glycogen Synthesis ◽

Glycolytic Flux ◽

Ampk Activation ◽

Ampk Activity ◽

Amp Activated Protein Kinase ◽

Isolated Rat

5′-AMP-activated protein kinase (AMPK) has been implicated in glycogen metabolism in skeletal muscle. However, the physiological relevance of increased AMPK activity during exercise has not been fully clarified. This study was performed to determine the direct effects of acute AMPK activation on muscle glycogen regulation. For this purpose, we used an isolated rat muscle preparation and pharmacologically activated AMPK with 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR). Tetanic contraction in vitro markedly activated the α1- and α2-isoforms of AMPK, with a corresponding increase in the rate of 3- O-methylglucose uptake. Incubation with AICAR elicited similar enhancement of AMPK activity and 3- O-methylglucose uptake in rat epitrochlearis muscle. In contrast, whereas contraction stimulated glycogen synthase (GS), AICAR treatment decreased GS activity. Insulin-stimulated GS activity also decreased after AICAR treatment. Whereas contraction activated glycogen phosphorylase (GP), AICAR did not alter GP activity. The muscle glycogen content decreased in response to contraction but was unchanged by AICAR. Lactate release was markedly increased when muscles were stimulated with AICAR in buffer containing glucose, indicating that the glucose taken up into the muscle was catabolized via glycolysis. Our results suggest that AMPK does not mediate contraction-stimulated glycogen synthesis or glycogenolysis in skeletal muscle and also that acute AMPK activation leads to an increased glycolytic flux by antagonizing contraction-stimulated glycogen synthesis.

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Regulation of glucose transport by the AMP-activated protein kinase

Proceedings of The Nutrition Society ◽

10.1079/pns2004340 ◽

2004 ◽

Vol 63 (2) ◽

pp. 205-210 ◽

Cited By ~ 24

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.

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Role of AMP-activated protein kinase in healthy and diseased hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00329.2006 ◽

2006 ◽

Vol 291 (6) ◽

pp. H2557-H2569 ◽

Cited By ~ 97

Author(s):

Vernon W. Dolinsky ◽

Jason R. B. Dyck

Keyword(s):

Energy Metabolism ◽

Protein Kinase ◽

Cardiac Myocyte ◽

Acid Oxidation ◽

Ampk Activation ◽

Cardiac Energy Metabolism ◽

Ampk Activity ◽

Cardiac Energy ◽

Metabolic Stresses ◽

Amp Activated Protein Kinase

The heart is capable of utilizing a variety of substrates to produce the necessary ATP for cardiac function. AMP-activated protein kinase (AMPK) has emerged as a key regulator of cellular energy homeostasis and coordinates multiple catabolic and anabolic pathways in the heart. During times of acute metabolic stresses, cardiac AMPK activation seems to be primarily involved in increasing energy-generating pathways to maintain or restore intracellular ATP levels. In acute situations such as mild ischemia or short durations of severe ischemia, activation of cardiac AMPK appears to be necessary for cardiac myocyte function and survival by stimulating ATP generation via increased glycolysis and accelerated fatty acid oxidation. Whereas AMPK activation may be essential for adaptation of cardiac energy metabolism to acute and/or minor metabolic stresses, it is unknown whether AMPK activation becomes maladaptive in certain chronic disease states and/or extreme energetic stresses. However, alterations in cardiac AMPK activity are associated with a number of cardiovascular-related diseases such as pathological cardiac hypertrophy, myocardial ischemia, glycogen storage cardiomyopathy, and Wolff-Parkinson-White syndrome, suggesting the possibility of a maladaptive role. Although the precise role AMPK plays in the diseased heart is still in question, it is clear that AMPK is a major regulator of cardiac energy metabolism. The consequences of alterations in AMPK activity and subsequent cardiac energy metabolism in the healthy and the diseased heart will be discussed.

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Sex Differences in Cardiac AMP-Activated Protein Kinase Following Exhaustive Exercise

Sports Medicine International Open ◽

10.1055/a-1115-6373 ◽

2020 ◽

Vol 4 (01) ◽

pp. E13-E18

Author(s):

Kevin D. Brown ◽

Edward D. Waggy ◽

Sreejayan Nair ◽

Timothy J. Robinson ◽

Emily E. Schmitt ◽

...

Keyword(s):

Heart Disease ◽

Protein Kinase ◽

Exhaustive Exercise ◽

Ampk Activation ◽

Ischemic Disease ◽

Specific Manner ◽

Ampk Activity ◽

Males And Females ◽

Amp Activated Protein Kinase ◽

The Impact

AbstractIschemic heart disease presents with significant differences between sexes. Endurance exercise protects the heart against ischemic disease and also distinctly impacts male and female patients through unidentified mechanisms, though some evidence implicates 5′-AMP-activated protein kinase (AMPK). The purpose of this investigation was to assess the impact of training and sex on cardiac AMPK activation following exhaustive exercise. AMPK activation was measured in trained and sedentary mice of both sexes. Trained mice ran on a treadmill at progressively increasing speeds and duration for 12 weeks. Trained and sedentary mice of both sexes were euthanized immediately following exhaustive exercise and compared to sedentary controls. Endurance training elicited adaptations indicative of aerobic adaptation including higher max running velocities and cardiac hypertrophy with no differences between males and females. AMPK activity was higher in male compared to females, and trained exhibited higher AMPK activity compared to sedentary mice. In response to training, male mice activated AMPK more robustly than female mice. Chronic exercise training increases the ability to activate cardiac AMPK in response to exhaustive exercise in a sex-specific manner. Understanding the interaction between exercise and sex is vital for use of exercise as medicine for heart disease in both men and women.

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Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin

Journal of Endocrinology ◽

10.1677/joe-06-0080 ◽

2007 ◽

Vol 192 (3) ◽

pp. 605-614 ◽

Cited By ~ 46

Author(s):

Fang Cai ◽

Armen V Gyulkhandanyan ◽

Michael B Wheeler ◽

Denise D Belsham

Keyword(s):

Protein Kinase ◽

Energy Homeostasis ◽

Cell Model ◽

Neuronal Cell ◽

Cell Types ◽

Glucose Sensing ◽

Protein Kinase Activity ◽

Energy Status ◽

Ampk Activity ◽

Amp Activated Protein Kinase

The mammalian hypothalamus comprises an array of phenotypically distinct cell types that interpret peripheral signals of energy status and, in turn, elicits an appropriate response to maintain energy homeostasis. We used a clonal representative hypothalamic cell model expressing proopiomelanocortin (POMC; N-43/5) to study changes in AMP-activated protein kinase (AMPK) activity and glucose responsiveness. We have demonstrated the presence of cellular machinery responsible for glucose sensing in the cell line, including glucokinase, glucose transporters, and appropriate ion channels. ATP-sensitive potassium channels were functional and responded to glucose. The N-43/5 POMC neurons may therefore be an appropriate cell model to study glucose-sensing mechanisms in the hypothalamus. In N-43/5 POMC neurons, increasing glucose concentrations decreased phospho-AMPK activity. As a relevant downstream effect, we found that POMC transcription increased with 2.8 and 16.7 mM glucose. Upon addition of leptin, with either no glucose or with 5 mM glucose, we found that leptin decreased AMPK activity in N-43/5 POMC neurons, but had no significant effect at 25 mM glucose, whereas insulin decreased AMPK activity at only 5 mM glucose. These results demonstrate that individual hypothalamic neuronal cell types, such as the POMC neuron, can have distinct responses to peripheral signals that relay energy status to the brain, and will therefore be activated uniquely to control neuroendocrine function.

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0358: Differential AMP-activated protein kinase (AMPK) activation in platelets, in response to various agonists. Comparison between human and murine platelets

Archives of Cardiovascular Diseases Supplements ◽

10.1016/s1878-6480(14)71420-x ◽

2014 ◽

Vol 6 ◽

pp. 57

Author(s):

Sophie Lepropre ◽

Marie-Blanche Onselaer ◽

Cécile Oury ◽

Luc Bertrand ◽

Jean-Louis Vanoverschelde ◽

...

Keyword(s):

Protein Kinase ◽

Ampk Activation ◽

Amp Activated Protein Kinase

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Adrenaline is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes

Biochemical Journal ◽

10.1042/bj20061479 ◽

2007 ◽

Vol 403 (3) ◽

pp. 473-481 ◽

Cited By ~ 81

Author(s):

Ho-Jin Koh ◽

Michael F. Hirshman ◽

Huamei He ◽

Yangfeng Li ◽

Yasuko Manabe ◽

...

Keyword(s):

Protein Kinase ◽

Protein Kinase Activity ◽

Chronic Exercise ◽

Rat Adipocytes ◽

Compound C ◽

Isolated Adipocytes ◽

Ampk Activity ◽

Exercise Induced ◽

Amp Activated Protein Kinase

Exercise increases AMPK (AMP-activated protein kinase) activity in human and rat adipocytes, but the underlying molecular mechanisms and functional consequences of this activation are not known. Since adrenaline (epinephrine) concentrations increase with exercise, in the present study we hypothesized that adrenaline activates AMPK in adipocytes. We show that a single bout of exercise increases AMPKα1 and α2 activities and ACC (acetyl-CoA carboxylase) Ser79 phosphorylation in rat adipocytes. Similarly to exercise, adrenaline treatment in vivo increased AMPK activities and ACC phosphorylation. Pre-treatment of rats with the β-blocker propranolol fully blocked exercise-induced AMPK activation. Increased AMPK activity with exercise and adrenaline treatment in vivo was accompanied by an increased AMP/ATP ratio. Adrenaline incubation of isolated adipocytes also increased the AMP/ATP ratio and AMPK activities, an effect blocked by propranolol. Adrenaline incubation increased lipolysis in isolated adipocytes, and Compound C, an AMPK inhibitor, attenuated this effect. Finally, a potential role for AMPK in the decreased adiposity associated with chronic exercise was suggested by marked increases in AMPKα1 and α2 activities in adipocytes from rats trained for 6 weeks. In conclusion, both acute and chronic exercise are significant regulators of AMPK activity in rat adipocytes. Our findings suggest that adrenaline plays a critical role in exercise-stimulated AMPKα1 and α2 activities in adipocytes, and that AMPK can function in the regulation of lipolysis.

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