Glucose metabolism in perfused mouse hearts overexpressing human GLUT-4 glucose transporter

2001 ◽  
Vol 280 (3) ◽  
pp. E420-E427 ◽  
Author(s):  
Darrel D. Belke ◽  
Terje S. Larsen ◽  
E. Michael Gibbs ◽  
David L. Severson
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Fatty Acid ◽  
Coronary Flow ◽  
Glucose Oxidation ◽  
Glucose Transporter ◽  
Acid Metabolism ◽  
Glut 4 ◽  
Cardiac Power ◽  
Glycolytic Rate

Glucose and fatty acid metabolism was assessed in isolated working hearts from control C57BL/KsJ- m+/+db mice and transgenic mice overexpressing the human GLUT-4 glucose transporter ( db/+-hGLUT-4). Heart rate, coronary flow, cardiac output, and cardiac power did not differ between control hearts and hearts overexpressing GLUT-4. Hearts overexpressing GLUT-4 had significantly higher rates of glucose uptake and glycolysis and higher levels of glycogen after perfusion than control hearts, but rates of glucose and palmitate oxidation were not different. Insulin (1 mU/ml) significantly increased glycogen levels in both groups. Insulin increased glycolysis in control hearts but not in GLUT-4 hearts, whereas glucose oxidation was increased by insulin in both groups. Therefore, GLUT-4 overexpression increases glycolysis, but not glucose oxidation, in the heart. Although control hearts responded to insulin with increased rates of glycolysis, the enhanced entry of glucose in the GLUT-4 hearts was already sufficient to maximally activate glycolysis under basal conditions such that insulin could not further stimulate the glycolytic rate.

scholarly journals Metabolic Profiling of Hearts Exposed to Sevoflurane and Propofol Reveals Distinct Regulation of Fatty Acid and Glucose Oxidation

2010 ◽  
Vol 113 (3) ◽  
pp. 541-551 ◽  
Author(s):  
Lianguo Wang ◽  
Kerry W. S. Ko ◽  
Eliana Lucchinetti ◽  
Liyan Zhang ◽  
Heinz Troxler ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Metabolism ◽  
Lipid Rafts ◽  
Metabolic Profiling ◽  
Glucose Oxidation ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Left Ventricular ◽  
Glucose Transporter 4 ◽  
Oxidative Energy Metabolism

Background Myocardial energy metabolism is a strong predictor of postoperative cardiac function. This study profiled the metabolites and metabolic changes in the myocardium exposed to sevoflurane, propofol, and Intralipid and investigated the underlying molecular mechanisms. Methods Sevoflurane (2 vol%) and propofol (10 and 100 microM) in the formulation of 1% Diprivan (AstraZeneca Inc., Mississauga, ON, Canada) were compared for their effects on oxidative energy metabolism and contractility in the isolated working rat heart model. Intralipid served as a control. Substrate flux through the major pathways for adenosine triphosphate generation in the heart, that is, fatty acid and glucose oxidation, was measured using [H]palmitate and [C]glucose. Biochemical analyses of nucleotides, acyl-CoAs, ceramides, and 32 acylcarnitine species were used to profile individual metabolites. Lipid rafts were isolated and used for Western blotting of the plasma membrane transporters CD36 and glucose transporter 4. Results Metabolic profiling of the hearts exposed to sevoflurane and propofol revealed distinct regulation of fatty acid and glucose oxidation. Sevoflurane selectively decreased fatty acid oxidation, which was closely related to a marked reduction in left ventricular work. In contrast, propofol at 100 microM but not 10 microM increased glucose oxidation without affecting cardiac work. Sevoflurane decreased fatty acid transporter CD36 in lipid rafts/caveolae, whereas high propofol increased pyruvate dehydrogenase activity without affecting glucose transporter 4, providing mechanisms for the fuel shifts in energy metabolism. Propofol increased ceramide formation, and Intralipid increased hydroxy acylcarnitine species. Conclusions Anesthetics and their solvents elicit distinct metabolic profiles in the myocardium, which may have clinical implications for the already jeopardized diseased heart.

Viability of the isolated soleus muscle during long-term incubation

2006 ◽  
Vol 31 (4) ◽  
pp. 467-476 ◽  
Author(s):  
Hakam Alkhateeb ◽  
Adrian Chabowski ◽  
Arend Bonen
Keyword(s):  
Fatty Acid ◽  
Protein Expression ◽  
Glucose Transport ◽  
Fatty Acid Metabolism ◽  
Soleus Muscle ◽  
Glucose Transporter ◽  
Acid Metabolism ◽  
Insulin Signalling ◽  
Low Concentrations

Skeletal muscle metabolism has been examined in perfused hindlimb muscles and in isolated muscle preparations. While long-term viability of the fast-twitch epitrochlearis has been documented with respect to glucose transport, it appears that long-term incubated soleus muscles are less stable when incubated ex vivo for many hours. Therefore, in the present study, we have examined whether the isolated soleus muscle remains metabolically viable for up to 18 h with respect to maintaining ATP and phosphocreatine (PCr) concentrations, carbohydrate and fatty-acid metabolism, insulin signalling, and protein expression. Soleus muscles were incubated in well-oxygenated Medium 199 (M199) supplemented with low concentrations of insulin (14.3 µU/mL) for 0, 6, 12, and 18 h. During this incubating period the concentrations of ATP and PCr were stable, indicating that oxygenation and substrate supply were being maintained. In addition, the concentrations of proglycogen and macroglycogen were not altered, whereas an increase (+30%) in intramuscular triacylglycerol concentration was observed at the end of 18 h of incubation (p < 0.05). Complex molecular processes in the long-term incubated muscles were also stable. This was shown by maintenance of basal as well as insulin-stimulated rates of 3-O-methyl glucose transport, and by the maintenance of protein expression of the glucose transporter GLUT4 and the fatty acid transporters FAT/CD36 and FABPpm. In addition, the insulin-stimulated translocation of GLUT4 to the plasma membrane, which involves a complex signalling cascade, was fully preserved. In conclusion, in well-oxygenated soleus muscles maintained in M199 supplemented with extremely low concentrations of insulin, ATP and PCr concentrations, carbohydrate and fatty acid metabolism, insulin signalling, and protein expression were stably maintained for up to 18 h. This provides for opportunities to examine muscle metabolic function under very highly controlled conditions.

Effect of excitement on coronary and systemic energetics in unanesthetized dogs

1965 ◽  
Vol 209 (4) ◽  
pp. 680-688 ◽  
Author(s):  
Claudia R. Rayford ◽  
Edward M. Khouri ◽  
Donald E. Gregg
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Coronary Flow ◽  
Cardiac Cycle ◽  
Myocardial Metabolism ◽  
Aortic Pressure ◽  
Moderate Increase ◽  
Sizeable Increase

The effect of excitement on phasic aortic pressure and flow, phasic left coronary flow, and myocardial metabolism has been studied in dogs 1–8 weeks after implantation of appropriate flowmeters and other devices. The rapid increase in heart rate and mild increase in blood pressure in the first few seconds tend to maintain coronary flow per minute despite a decrease in stroke cardiac output and coronary flow throughout the cardiac cycle. The main response is a delayed rise in coronary flow per minute resulting from further elevation of heart rate and blood pressure, a moderate increase in stroke cardiac output and a sizeable increase in stroke coronary flow, the latter being divided fairly evenly between systole and diastole. From 60 to 90% of the increase in mean coronary flow arises from the increase in stroke coronary flow, and the remainder from the increased number of heartbeats per minute. Some of the possible mechanisms concerned are discussed.

A Method to Personalize the Lumped Parameter Model of Coronary Artery

2019 ◽  
Vol 16 (03) ◽  
pp. 1842004 ◽  
Author(s):  
Bao Li ◽  
Wenxin Wang ◽  
Boyan Mao ◽  
Youjun Liu
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Coronary Artery ◽  
Coronary Flow ◽  
Systemic Circulation ◽  
Aortic Pressure ◽  
Physiological Parameters ◽  
Lumped Parameter Model ◽  
Non Invasive ◽  
Lumped Parameter

A method which can personalize the lumped parameter model of coronary artery and cardiovascular system based on the non-invasive physiological parameters has been developed. The parameters of system were determined by different physiological parameters. The heart module was determined by aortic pressure and heart rate; the systemic circulation module was determined by cardiac output, height and cardio-ankle vascular index (CAVI), while the CAVI was determined by age and aortic pressure; the coronary module was determined by the target waveforms of coronary flow rate predicted from cardiac output. The considerable results proved that this method could be applied to each patient.

Abstract 17827: Klf5 Mediates Glucose-driven Changes ofCcardiac Pparα in Diabetes

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Konstantinos Drosatos ◽  
Nina M Pollak ◽  
Florian Willecke ◽  
Panagiotis Ntziachristos ◽  
Chad M Trent ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Plasma Glucose ◽  
Binding Sites ◽  
Glucose Transporter ◽  
Acid Metabolism ◽  
In Silico Analysis ◽  
Dependent Manner ◽  
Glucose Transporter 2

Krüppel-like factors (KLF) affect metabolism. Lipopolysaccharide-induced sepsis reduced cardiac PPARα and increased KLF5 (8-fold) more than any cardiac KLF isoform detected by whole genome microarray analysis. In silico analysis of ppara gene promoter predicted two KLF5 binding sites that overlap with c-Jun (AP-1) binding sites: -792/-772 bp and -719/-698 bp. Infection of a mouse cardiomyocyte cell line (HL-1) with adenovirus expressing constitutively active c-Jun reduced, while Ad-KLF5 increased PPARα mRNA in a dose-dependent manner. Chromatin immunoprecipitation (ChIP) showed that c-Jun binds both -792/-772 bp and -719/-698 on ppara promoter while KLF5 binds on -792/-772 bp. ChIP on LPS-treated HL-1 cells showed that c-Jun binding on -792/-772 bp prohibits KLF5 binding. We generated a cardiomyocyte-specific KLF5 knockout mouse (αMHC-KLF5-/-), which had 50% normal cardiac function. Cardiomyocyte-specific KLF5 ablation reduced PPARα (50%) and several fatty acid metabolism-associated genes such as CD36 (40%), LpL (20%), PGC1α (45%), AOX (28%) and Cpt1 (45%). As PPARα regulates cardiac fatty acid metabolism, we tested whether cardiac KLF5 is modulated in diabetes, when cardiac PPARα and lipid changes occur. I.p. injection of streptozotocin (STZ) in C57BL/6 mice increased plasma glucose (2.9-fold) and reduced cardiac KLF5 and PPARα gene expression; similar to STZ-treated rats but unlike what had been found in a different mouse strain (C57BL/6 x DBA2) treated with STZ. Treatment of HL-1 cells with increased glucose-containing medium (1 mg/ml) reduced KLF5 (80%) and PPARα (65%), as well as fatty acid metabolism markers, such as AOX (85%), Cpt1β (70%), LCAD (80%) and VLCAD (85%). On the other hand GLUT1 and GLUT4 were increased (30% and 20%) and PDK4 was reduced (65%) indicating increased glucose utilization. A model of non-insulin dependent hyperglycemia (ob/ob mice) had reduced cardiac KLF5 (60%) and PPARα (65%). Correction of hyperglycemia in STZ-treated C57BL/6 mice by pharmacological (dapagliflozin) or antisense oligonucleotide inhibition of kidney’s sodium glucose transporter 2 (SGLT2), restored KLF5 and PPARα gene expression. Thus, KLF5 is a transcriptional regulator of cardiac PPARα that is driven by changes in plasma glucose levels

Glucose and fatty acid metabolism in the isolated working mouse heart

1999 ◽  
Vol 277 (4) ◽  
pp. R1210-R1217 ◽  
Author(s):  
Darrell D. Belke ◽  
Terje S. Larsen ◽  
Gary D. Lopaschuk ◽  
David L. Severson
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Glucose Utilization ◽  
Acid Metabolism ◽  
Acid Oxidation ◽  
Mouse Heart ◽  
Mechanical Function ◽  
Substrate Metabolism ◽  
Cardiac Power ◽  
Rat Hearts

Although isolated perfused mouse heart models have been developed to study mechanical function, energy substrate metabolism has not been examined despite the expectation that the metabolic rate for a heart from a small mammal should be increased. Consequently, glucose utilization (glycolysis, oxidation) and fatty acid oxidation were measured in isolated working mouse hearts perfused with radiolabeled substrates, 11 mM glucose, and either 0.4 or 1.2 mM palmitate. Heart rate, coronary flow, cardiac output, and cardiac power did not differ significantly between hearts perfused at 0.4 or 1.2 mM palmitate. Although the absolute values obtained for glycolysis and glucose oxidation and fatty acid oxidation are significantly higher than those reported for rat hearts, the pattern of substrate metabolism in mouse hearts is similar to that observed in hearts from larger mammals. The metabolism of mouse hearts can be altered by fatty acid concentration in a manner similar to that observed in larger animals; increasing palmitate concentration altered the balance of substrate metabolism to increase overall energy derived from fatty acids from 64 to 92%.

scholarly journals Gravity Threshold and Dose Response Relationships: Health Benefits Using a Short Arm Human Centrifuge

2021 ◽  
Vol 12 ◽  
Author(s):  
Chrysoula Kourtidou-Papadeli ◽  
Christos A. Frantzidis ◽  
Sotiria Gilou ◽  
Christina E. Plomariti ◽  
Christiane M. Nday ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Cardiac Output ◽  
Dose Response ◽  
Neuromuscular Disorders ◽  
Male And Female ◽  
Cardiovascular Parameters ◽  
Cardiac Power ◽  
Cardiovascular Evaluation

PurposeIncreasing the level of gravity passively on a centrifuge, should be equal to or even more beneficial not only to astronauts living in a microgravity environment but also to patients confined to bed. Gravity therapy (GT) may have beneficial effects on numerous conditions, such as immobility due to neuromuscular disorders, balance disorders, stroke, sports injuries. However, the appropriate configuration for administering the Gz load remains to be determined.MethodsTo address these issues, we studied graded G-loads from 0.5 to 2.0g in 24 young healthy, male and female participants, trained on a short arm human centrifuge (SAHC) combined with mild activity exercise within 40–59% MHR, provided by an onboard bicycle ergometer. Hemodynamic parameters, as cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were analyzed, as well as blood gas analysis. A one-way repeated measures ANOVA and pairwise comparisons were conducted with a level of significance p &lt; 0.05.ResultsSignificant changes in heart rate variability (HRV) and its spectral components (Class, Fmax, and VHF) were found in all g loads when compared to standing (p &lt; 0.001), except in 1.7 and 2.0g. There were significant changes in CO, cardiac index (CI), and cardiac power (CP) (p &lt; 0.001), and in MAP (p = 0.003) at different artificial gravity (AG) levels. Dose-response curves were determined based on statistically significant changes in cardiovascular parameters, as well as in identifying the optimal G level for training, as well as the optimal G level for training. There were statistically significant gender differences in Cardiac Output/CO (p = 0.002) and Cardiac Power/CP (p = 0.016) during the AG training as compared to standing. More specifically, these cardiovascular parameters were significantly higher for male than female participants. Also, there was a statistically significant (p = 0.022) gender by experimental condition interaction, since the high-frequency parameter of the heart rate variability was attenuated during AG training as compared to standing but only for the female participants (p = 0.004).ConclusionThe comprehensive cardiovascular evaluation of the response to a range of graded AG loads, as compared to standing, in male and female subjects provides the dose-response framework that enables us to explore and validate the usefulness of the centrifuge as a medical device. It further allows its use in precisely selecting personalized gravity therapy (GT) as needed for treatment or rehabilitation of individuals confined to bed.

Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels

1987 ◽  
Vol 252 (5) ◽  
pp. E648-E653 ◽  
Author(s):  
V. Hingorani ◽  
P. Brecher
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Cholesterol Ester ◽  
Glucose Oxidation ◽  
Acid Metabolism ◽  
Lactate Production ◽  
Acid Oxidation ◽  
Cerebral Microvessels ◽  
Diabetic Rabbits

Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either [6-14C]glucose or [1-14C]oleic acid and the incorporation of radioactivity into 14CO2, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO2 was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to 14CO2 was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO2 and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously.

Cardiovascular functions during voluntary apnea in dogs

1983 ◽  
Vol 245 (2) ◽  
pp. R143-R150
Author(s):  
Y. C. Lin ◽  
E. L. Carlson ◽  
E. P. McCutcheon ◽  
H. Sandler
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Myocardial Contractility ◽  
Peripheral Resistance ◽  
Cardiac Pacing ◽  
Cardiovascular Responses ◽  
Active Role ◽  
Left Ventricular ◽  
Stroke Work ◽  
Cardiac Power

We studied cardiovascular responses to apnea during voluntary snout immersion in conscious, chronically instrumented dogs. Voluntary snout immersion up to eye level for a duration of greater than 15 s ensured that the dog was engaged in active apnea. In a control apnea of 15-35 s, heart rate decreased by 43% from a control value of 104 beats/min. Changes in cardiac output paralleled those of heart rate. Mean aortic blood pressure did not vary during apnea, which, coupled with a reduced cardiac output, indicated a 65% increase in estimated total peripheral resistance compared with preapnea values. Treatment with atropine sulfate (0.2 mg/kg) eliminated the bradycardia response, but the peripheral vasoconstriction persisted. Treatment with propranolol (0.5 mg/kg) eliminated postapnea hypertension. Changes in myocardial contractility during apnea were observed by measuring hemodynamic parameters while maintaining a constant heart rate with cardiac pacing. Myocardial contractility was decreased during apnea as indicated by decreases in stroke volume (-13%), stroke work (-22%), cardiac output (-13%), left ventricular (dP/dt)max (-11%), and cardiac power (-24%). These changes were prevented by atropine treatment, indicating the depressed contractility was a result of vagus nerve activity. The circulatory adjustments in the dog during apnea are potential mechanisms for oxygen conservation, although the effectiveness is uncertain for the animal as a whole. It is clear that by appropriate reduction in cardiac power output, the heart itself plays an active role in conservation of limited oxygen during apnea.

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