scholarly journals Qiliqiangxin Enhances Cardiac Glucose Metabolism and Improves Diastolic Function in Spontaneously Hypertensive Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jingfeng Wang ◽  
Zhiming Li ◽  
Yanyan Wang ◽  
Jingjing Zhang ◽  
Weipeng Zhao ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Diastolic Function ◽  
Spontaneously Hypertensive Rat ◽  
Small Animal ◽  
Small Animal Pet ◽  
Spontaneously Hypertensive ◽  
Key Enzymes ◽  
Atp Production ◽  
Myocardial Glucose Uptake

Cardiac diastolic dysfunction has emerged as a growing type of heart failure. The present study aims to explore whether Qiliqiangxin (QL) can benefit cardiac diastolic function in spontaneously hypertensive rat (SHR) through enhancement of cardiac glucose metabolism. Fifteen 12-month-old male SHRs were randomly divided into QL-treated, olmesartan-treated, and saline-treated groups. Age-matched WKY rats served as normal controls. Echocardiography and histological analysis were performed. Myocardial glucose uptake was determined by 18F-FDG using small-animal PET imaging. Expressions of several crucial proteins and key enzymes related to glucose metabolism were also evaluated. As a result, QL improved cardiac diastolic function in SHRs, as evidenced by increased E′/A′and decreased E/E′ (P<0.01). Meanwhile, QL alleviated myocardial hypertrophy, collagen deposits, and apoptosis (P<0.01). An even higher myocardial glucose uptake was illustrated in QL-treated SHR group (P<0.01). Moreover, an increased CS activity and ATP production was observed in QL-treated SHRs (P<0.05). QL enhanced cardiac glucose utilization and oxidative phosphorylation in SHRs by upregulating AMPK/PGC-1α axis, promoting GLUT-4 expression, and regulating key enzymes related to glucose aerobic oxidation such as HK2, PDK4, and CS (P<0.01). Our data suggests that QL improves cardiac diastolic function in SHRs, which may be associated with enhancement of myocardial glucose metabolism.

Abstract 3305: FDG PET Imaging in the PRKAG2 Cardiac Syndrome Demonstrates Altered Myocardial Glucose Uptake

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Andrew C Ha ◽  
Jennifer Renaud ◽  
Stephanie Thorn ◽  
Rob deKemp ◽  
Keiichiro Yoshinaga ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Pet Imaging ◽  
Plasma Glucose ◽  
Fdg Pet ◽  
Adult Patients ◽  
Myocardial Glucose Uptake ◽  
Cardiac Syndrome ◽  
The Mean ◽  
Normal Controls

Background : The PRKAG2 gene encodes for the gamma-2 subunit of AMP-activated protein kinase (AMPK), a protein implicated in the regulation of myocardial glucose metabolism. In humans, mutations of the PRKAG2 gene result in a cardiomyopathy characterized by ventricular pre-excitation, atrioventricular conduction disease, and cardiac hypertrophy. It is recognized that altered cardiac glucose metabolism and abnormal glycogen stores are responsible for the clinical manifestations of this syndrome. Since myocardial glucose uptake can be measured with 2-[ 18 F]Fluoro-2-deoxyglucose dynamic positron emission tomography ([ 18 F]FDG PET), we examined whether adult patients with an identified Arg302Gln PRKAG2 mutation have altered myocardial glucose uptake using this imaging modality. Methods: [ 18 F]FDG PET was performed in 5 adult patients with the Arg302Gln PRKAG2 mutation (PRKAG2) and in 6 healthy volunteers (Control) with a hyperinsulinemic euglycemic clamp protocol. The fractional rate of radiotracer uptake (K) is derived from PATLAK analysis. The rate of myocardial glucose uptake (rMGU) of the left ventricle (LV) is calculated as (K / LC) x P glucose , where P glucose represents the mean plasma glucose level during imaging. LC (lump constant) corrects for the differences in the transport and phosphorylation of [ 18 F]FDG and glucose. Results are expressed as mean ± standard deviation and are analyzed with the student t-test. Results: The mean rMGU in the PRKAG2 group was significantly lower than the control group. There was no difference in the mean plasma glucose levels between the 2 groups. (Table ) Conclusion: Myocardial glucose uptake is reduced in adult patients with mutation of the PRKAG2 gene when compared to normal controls. Measurement of rMGU using [ 18 F]FDG PET imaging appears to be a useful tool to investigate the pathophysiology of the PRKAG2 cardiac syndrome and to potentially distinguish this metabolic cardiomyopathy from other etiolgies. Mean rate of myocardial glucose uptake between patients with the PRKAG2 mutation and normal controls

Ranolazine Improves Diastolic Function in the Stress-Tested Spontaneously Hypertensive Rat

Heart Rhythm ◽  
2012 ◽  
Vol 9 (11) ◽  
pp. 1915-1916 ◽  
Author(s):  
M. Pourrier ◽  
S. Williams ◽  
B. Allison ◽  
D. McAfee ◽  
D. Fedida
Keyword(s):  
Diastolic Function ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat

scholarly journals Transgenic and Recombinant Resistin Impair Skeletal Muscle Glucose Metabolism in the Spontaneously Hypertensive Rat

2003 ◽  
Vol 278 (46) ◽  
pp. 45209-45215 ◽  
Author(s):  
Michal Pravenec ◽  
Ludmila Kazdová ◽  
Vladimír Landa ◽  
Václav Zídek ◽  
Petr Mlejnek ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Spontaneously Hypertensive Rat ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat

Inhibition of myocardial glucose uptake by cGMP

1998 ◽  
Vol 274 (5) ◽  
pp. H1443-H1449 ◽  
Author(s):  
Christophe Depre ◽  
Vinciane Gaussin ◽  
Sylvie Ponchaut ◽  
Yvan Fischer ◽  
Jean-Louis Vanoverschelde ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Acid Oxidation ◽  
No Production ◽  
Heart Metabolism ◽  
No Donor ◽  
Myocardial Glucose Uptake ◽  
Cyclic Monophosphate ◽  
Heart Work ◽  
Cgmp Analog

Guanosine 3′,5′-cyclic monophosphate (cGMP), a second messenger of nitric oxide (NO), regulates myocardial contractility. It is not known whether this effect is accompanied by a change in heart metabolism. We report here the effects of 8-bromoguanosine 3′,5′-cyclic monophosphate (8-BrcGMP), a cGMP analog, on regulatory steps of glucose metabolism in isolated working rat hearts perfused with glucose as the substrate. When glucose uptake was stimulated by increasing the workload, addition of the cGMP analog totally suppressed this stimulation and accelerated net glycogen breakdown. 8-BrcGMP did not affect pyruvate dehydrogenase activity but activated acetyl-CoA carboxylase, the enzyme that produces malonyl-CoA, an inhibitor of long-chain fatty acid oxidation. To test whether glucose metabolism could also be affected by altering the intracellular concentration of cGMP, we perfused hearts with N G-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase, or with S-nitroso- N-acetylpenicillamine (SNAP), a NO donor. Perfusion withl-NAME decreased cGMP and increased glucose uptake by 30%, whereas perfusion with SNAP resulted in opposite effects. None of these conditions affected adenosine 3′,5′-cyclic monophosphate concentration. Limitation of glucose uptake by SNAP or 8-BrcGMP decreased heart work, and this was reversed by adding alternative oxidizable substrates (pyruvate, β-hydroxybutyrate) together with glucose. Therefore, increased NO production decreases myocardial glucose utilization and limits heart work. This effect is mediated by cGMP, which is thus endowed with both physiological and metabolic properties.

scholarly journals SGK1 Signaling Promotes Glucose Metabolism and Survival in Extracellular Matrix Detached Cells

2020 ◽  
Author(s):  
Joshua A. Mason ◽  
Jordan A. Cockfield ◽  
Daniel J. Pape ◽  
Hannah Meissner ◽  
Michael Sokolowski ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Death ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Carbon Flux ◽  
Pentose Phosphate ◽  
Atp Production ◽  
Elevated Glucose ◽  
Atp Generation ◽  
Necessary And Sufficient

SummaryLoss of integrin-mediated attachment to extracellular matrix (ECM) proteins can trigger a variety of cellular changes that impact cell viability. Foremost among these is the activation of anoikis, caspase-mediated cell death induced by ECM-detachment. In addition to anoikis, loss of ECM-attachment causes profound alterations in cellular metabolism that can lead to anoikis-independent cell death. Here, we describe a surprising role for serum and glucocorticoid kinase-1 (SGK1) in the promotion of energy production when cells are detached. Our data demonstrate that SGK1 activation is necessary and sufficient for ATP generation during ECM-detachment and anchorage-independent growth. More specifically, SGK1 promotes a substantial elevation in glucose uptake due to elevated GLUT1 transcription. In addition, carbon flux into the pentose phosphate pathway (PPP) is necessary to accommodate elevated glucose uptake and PPP-mediated glyceraldehyde-3-phosphate (G3P) is necessary for ATP production. Thus, our data unmask SGK1 as master regulator of glucose metabolism and cell survival during ECM-detached conditions.

scholarly journals Simvastatin profoundly impairs energy metabolism in primary human muscle cells

2020 ◽  
Vol 9 (11) ◽  
pp. 1103-1113
Author(s):  
Selina Mäkinen ◽  
Neeta Datta ◽  
Yen H Nguyen ◽  
Petro Kyrylenko ◽  
Markku Laakso ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Human Skeletal Muscle ◽  
Insulin Signalling ◽  
Glycogen Synthesis ◽  
Muscle Cells ◽  
Acid Form ◽  
Lactone Form ◽  
Atp Production ◽  
Human Skeletal Muscle Cells

Objectives Simvastatin use is associated with muscular side effects, and increased risk for type 2 diabetes (T2D). In clinical use, simvastatin is administered in inactive lipophilic lactone-form, which is then converted to active acid-form in the body. Here, we have investigated if lactone- and acid-form simvastatin differentially affect glucose metabolism and mitochondrial respiration in primary human skeletal muscle cells. Methods Muscle cells were exposed separately to lactone- and acid-form simvastatin for 48 h. After pre-exposure, glucose uptake and glycogen synthesis were measured using radioactive tracers; insulin signalling was detected with Western blotting; and glycolysis, mitochondrial oxygen consumption and ATP production were measured with Seahorse XFe96 analyzer. Results Lactone-form simvastatin increased glucose uptake and glycogen synthesis, whereas acid-form simvastatin did not affect glucose uptake and decreased glycogen synthesis. Phosphorylation of insulin signalling targets Akt substrate 160 kDa (AS160) and glycogen synthase kinase 3β (GSK3β) was upregulated with lactone-, but not with acid-form simvastatin. Exposure to both forms of simvastatin led to a decrease in glycolysis and glycolytic capacity, as well as to a decrease in mitochondrial respiration and ATP production. Conclusions These data suggest that lactone- and acid-forms of simvastatin exhibit differential effects on non-oxidative glucose metabolism as lactone-form increases and acid-form impairs glucose storage into glycogen, suggesting impaired insulin sensitivity in response to acid-form simvastatin. Both forms profoundly impair oxidative glucose metabolism and energy production in human skeletal muscle cells. These effects may contribute to muscular side effects and risk for T2D observed with simvastatin use.

Impaired ATP turnover and ADP supply depress cardiac mitochondrial respiration and elevate superoxide in nonfailing spontaneously hypertensive rat hearts

2009 ◽  
Vol 297 (3) ◽  
pp. C766-C774 ◽  
Author(s):  
Anthony J. R. Hickey ◽  
Chau C. Chai ◽  
Soon Y. Choong ◽  
Silvana de Freitas Costa ◽  
Gretchen L. Skea ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Complex I ◽  
Atp Hydrolysis ◽  
Spontaneously Hypertensive Rat ◽  
Ex Vivo ◽  
Cardiac Mitochondria ◽  
Spontaneously Hypertensive ◽  
Atp Production ◽  
Atp Turnover ◽  
Wistar Kyoto

Although most attention has been focused on mitochondrial ATP production and transfer in failing hearts, less has been focused on the nonfailing hypertensive heart. Here, energetic complications are less obvious, yet they may provide insight into disease ontogeny. We studied hearts from 12-mo-old spontaneously hypertensive rats (SHR) relative to normotensive Wistar-Kyoto (WKY) rats. The ex vivo working-heart model of SHR showed reduced compliance and impaired responses to increasing preloads. High-resolution respirometry showed higher state 3 (with excess ADP) respiration in SHR left ventricle fibers with complex I substrates and maximal uncoupled respiration with complex I + complex II substrates. Respiration with ATP was depressed 15% in SHR fibers relative to WKY fibers, suggesting impaired ATP hydrolysis. This finding was consistent with a 50% depression of actomyosin ATPase activities. Superoxide production from SHR fibers was similar to that from WKY fibers respiring with ADP; however, it was increased by 15% with ATP. In addition, the apparent Km for ADP was 54% higher for SHR fibers, and assays conducted after ex vivo work showed a 28% depression of complex I in SHR, but not WKY, fibers. Transmission electron microscopy showed similar mitochondrial volumes but a decrease in the number of cristae in SHR mitochondria. Tissue lipid peroxidation was also 15% greater in SHR left ventricle. Overall, these data suggest that although cardiac mitochondria from nonfailing SHR hearts function marginally better than those from WKY hearts, they show dysfunction after intense work. Impaired ATP turnover in hard-working SHR hearts may starve cardiac mitochondria of ADP and elevate superoxide.

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