Role of glucose metabolism in the recovery of postischemic LV mechanical function: effects of insulin and other metabolic modulators

2008 ◽  
Vol 294 (6) ◽  
pp. H2576-H2586 ◽  
Author(s):  
Manoj Gandhi ◽  
Barry A. Finegan ◽  
Alexander S. Clanachan
Keyword(s):  
Glucose Metabolism ◽  
Glucose Oxidation ◽  
Recovery Of Function ◽  
Mechanical Function ◽  
Rat Hearts ◽  
Inhibition Of Glycolysis ◽  
Simultaneous Inhibition ◽  
Optimal Protection

The role of proton (H+) production from glucose metabolism in the recovery of myocardial function during postischemic reperfusion and its alteration by insulin and other metabolic modulators were examined. Rat hearts were perfused in vitro with Krebs-Henseleit solution containing palmitate (1.2 mmol/l) and glucose (11 mmol/l) under nonischemic conditions or during reperfusion following no-flow ischemia. Perfusate contained normal insulin (n-Ins, 50 mU/l), zero insulin (0-Ins), or supplemental insulin (s-Ins, 1,000 mU/l) or other metabolic modulators [dichloroacetate (DCA) at 3 mmol/l, oxfenicine at 1 mmol/l, and N6-cyclohexyladenosine (CHA) at 0.5 μmol/l]. Relative to n-Ins, 0-Ins depressed rates of glycolysis and glucose oxidation in nonischemic hearts and impaired recovery of postischemic function. Relative to n-Ins, s-Ins did not affect aerobic glucose metabolism and did not improve recovery when present during reperfusion. When present during ischemia and reperfusion, s-Ins impaired recovery. Combinations of metabolic modulators with s-Ins stimulated glucose oxidation ∼2.5-fold in nonischemic hearts and reduced H+ production. DCA and CHA, in combination with s-Ins, improved recovery of function, but addition of oxfenicine to this combination provided no further benefit. Although DCA and CHA were each partially protective in hearts perfused with n-Ins, optimal protection was achieved with DCA + CHA; recovery of function was inversely proportional to H+ production during reperfusion. Although supplemental insulin is not beneficial, elimination of H+ production from glucose metabolism by simultaneous inhibition of glycolysis and stimulation of glucose oxidation optimizes recovery of postischemic mechanical function.

Ischemic preconditioning inhibits glycolysis and proton production in isolated working rat hearts

1995 ◽  
Vol 269 (5) ◽  
pp. H1767-H1775 ◽  
Author(s):  
B. A. Finegan ◽  
G. D. Lopaschuk ◽  
M. Gandhi ◽  
A. S. Clanachan
Keyword(s):  
Ischemic Preconditioning ◽  
Glucose Oxidation ◽  
Glycogen Content ◽  
Enhanced Recovery ◽  
Adenine Nucleotide ◽  
Ischemia And Reperfusion ◽  
Mechanical Function ◽  
Proton Production ◽  
Rat Hearts ◽  
Inhibition Of Glycolysis

The effect of ischemic preconditioning (IPC) on glycolysis, glucose oxidation, adenine nucleotide and nucleoside levels, and mechanical function was studied in isolated paced working rat hearts under aerobic conditions or when reperfused following sustained ischemia. IPC inhibited glycolysis in aerobic hearts (4.48 +/- 0.66 vs. 3.18 +/- 0.39 mumol.min-1.g dry wt-1) and calculated proton production attributable to exogenous glucose (7.79 +/- 1.31 vs. 4.73 +/- 0.81 mumol.min-1.g dry wt-1). In hearts subjected to ischemia and reperfusion, IPC decreased, relative to controls, glycogen content before the onset of ischemia (116.6 +/- 4.3 vs. 158.0 +/- 8.4 mumol/dry wt) and decreased consumption of glycogen during ischemia (54 +/- 6 vs. 76 +/- 7 mumol/dry wt). During reperfusion, glycolysis was lower in IPC hearts (2.45 +/- 0.16 vs. 4.4 +/- 0.46 mumol.min-1.g dry wt-1), as was calculated proton production (3.57 +/- 0.30 vs. 8.38 +/- 0.93 mumol.min-1.g dry wt-1). Glucose oxidation was similar in control and IPC hearts. Adenosine and ATP content of IPC hearts, relative to controls, were higher at the end of ischemia, being 0.86 +/- 0.08 vs. 0.34 +/- 0.15 mumol/g dry wt and 11.3 +/- 0.8 vs. 5.0 +/- 1.6 mumol/g dry wt, respectively. IPC enhanced recovery of ventricular work during reperfusion of ischemic hearts from 37 to 68%. These results indicate that IPC is associated with a reduction in glycogen content, inhibition of glycolysis during ischemia and reperfusion, and a decrease in proton production from glucose. These changes may, in part, explain the enhanced recovery of mechanical function observed in IPC hearts.

scholarly journals Author Correction: Simultaneous Inhibition of Glycolysis and Oxidative Phosphorylation Triggers a Multi-Fold Increase in Secretion of Exosomes: Possible Role of 2′,3′-cAMP

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nils Ludwig ◽  
Saigopalakrishna S. Yerneni ◽  
Elizabeth V. Menshikova ◽  
Delbert G. Gillespie ◽  
Edwin K. Jackson ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Fold Increase ◽  
Inhibition Of Glycolysis ◽  
Simultaneous Inhibition

scholarly journals Simultaneous Inhibition of Glycolysis and Oxidative Phosphorylation Triggers a Multi-Fold Increase in Secretion of Exosomes: Possible Role of 2′,3′-cAMP

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nils Ludwig ◽  
Saigopalakrishna S. Yerneni ◽  
Elizabeth V. Menshikova ◽  
Delbert G. Gillespie ◽  
Edwin K. Jackson ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Fold Increase ◽  
Inhibition Of Glycolysis ◽  
Simultaneous Inhibition

Intrinsic ANG II type 1 receptor stimulation contributes to recovery of postischemic mechanical function

1998 ◽  
Vol 274 (5) ◽  
pp. H1524-H1531 ◽  
Author(s):  
William R. Ford ◽  
Alexander S. Clanachan ◽  
Gary D. Lopaschuk ◽  
Richard Schulz ◽  
Bodh I. Jugdutt
Keyword(s):  
Recovery Of Function ◽  
Left Ventricular ◽  
Dependent Manner ◽  
Mechanical Function ◽  
Ang Ii ◽  
Concentration Dependent Manner ◽  
Proton Production ◽  
Rat Hearts ◽  
Postischemic Recovery

To determine whether intrinsic angiotensin II (ANG II) type 1 receptor (AT1-R) stimulation modulates recovery of postischemic mechanical function, we studied the effects of selective AT1-R blockade with losartan on proton production from glucose metabolism and recovery of function in isolated working rat hearts perfused with Krebs-Henseleit buffer containing palmitate, glucose, and insulin. Aerobic perfusion (50 min) was followed by global, no-flow ischemia (30 min) and reperfusion (30 min) in the presence ( n = 10) or absence ( n = 14) of losartan (1 μmol/l) or the cardioprotective adenosine A1receptor agonist N 6-cyclohexyladenosine (CHA, 0.5 μmol/l, n = 11). During reperfusion in untreated hearts (controls), left ventricular (LV) minute work partially recovered to 38% of aerobic baseline, whereas proton production increased to 155%. Compared with controls, CHA improved recovery of LV work to 79% and reduced proton production to 44%. Losartan depressed recovery of LV work to 0% without altering proton production. However, exogenous ANG II (1–100 nmol/l) in combination with losartan restored recovery of LV work during reperfusion in a concentration-dependent manner, suggesting that postischemic recovery of function depends on intrinsic AT1-R stimulation.

Dichloroacetate improves cardiac efficiency after ischemia independent of changes in mitochondrial proton leak

2001 ◽  
Vol 280 (4) ◽  
pp. H1762-H1769 ◽  
Author(s):  
Masayuki Taniguchi ◽  
Craig Wilson ◽  
Charlene A. Hunter ◽  
Daniel J. Pehowich ◽  
Alexander S. Clanachan ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Glucose Metabolism ◽  
Pyruvate Dehydrogenase ◽  
Mitochondrial Membrane ◽  
Glucose Oxidation ◽  
Proton Leak ◽  
Cardiac Efficiency ◽  
Cardiac Work ◽  
Atp Production ◽  
Rat Hearts

Dichloroacetate (DCA) is a pyruvate dehydrogenase activator that increases cardiac efficiency during reperfusion of ischemic hearts. We determined whether DCA increases efficiency of mitochondrial ATP production by measuring proton leak in mitochondria from isolated working rat hearts subjected to 30 min of ischemia and 60 min of reperfusion. In untreated hearts, cardiac work and efficiency decreased during reperfusion to 26% and 40% of preischemic values, respectively. Membrane potential was significantly lower in mitochondria from reperfused (175.6 ± 2.2 mV) versus aerobic (185.8 ± 3.1 mV) hearts. DCA (1 mM added at reperfusion) improved recovery of cardiac work (1.9-fold) and efficiency (1.5-fold) but had no effect on mitochondrial membrane potential (170.6 ± 2.9 mV). At the maximal attainable membrane potential, O2consumption (nmol O2 · mg−1 · min−1) did not differ between untreated or DCA-treated hearts (128.3 ± 7.5 and 120.6 ± 7.6, respectively) but was significantly greater than aerobic hearts (76.6 ± 7.6). During reperfusion, DCA increased glucose oxidation 2.5-fold and decreased H+production from glucose metabolism to 53% of untreated hearts. Because H+ production decreases cardiac efficiency, we suggest that DCA increases cardiac efficiency during reperfusion of ischemic hearts by increasing the efficiency of ATP use and not by increasing the efficiency of ATP production.

Dichloroacetate stimulation of glucose oxidation improves recovery of ischemic rat hearts

1990 ◽  
Vol 259 (4) ◽  
pp. H1079-H1085 ◽  
Author(s):  
J. J. McVeigh ◽  
G. D. Lopaschuk
Keyword(s):  
Fatty Acid ◽  
Glucose Oxidation ◽  
Acid Inhibition ◽  
Mechanical Function ◽  
Oxidation Rates ◽  
Rat Hearts ◽  
High Concentrations ◽  
Fatty Acid Inhibition ◽  
Mechanical Recovery ◽  
Stimulation Of

We have previously shown that high concentrations of fatty acids depress reperfusion recovery of ischemic rat hearts as a result of a fatty acid inhibition of glucose oxidation. In this study, we determined whether dichloroacetate, an activator of pyruvate dehydrogenase, could overcome fatty acid inhibition of glucose oxidation and thereby improve mechanical recovery of hearts reperfused after a period of transient global ischemia. Isolated working rat hearts, perfused with 11 mM glucose, 1.2 mM palmitate, and 500 microU/ml insulin, were subjected to a 30-min period of no flow ischemia, followed by a 30-min period of reperfusion. Under these conditions, control hearts recovered 37% of preischemic function. The addition of 1 mM dichloroacetate to the perfusate at reperfusion resulted in a significant improvement in recovery of mechanical function (to 73% of preischemic function). When dichloroacetate was added before the onset of ischemia, however, this protective effect was lost, and a significant increase in myocardial lactate accumulation during ischemia was observed. The effects of dichloroacetate on glucose oxidation rates in both nonischemic and reperfused ischemic hearts was determined by perfusing hearts with 11 mM [U-14C]glucose and 1.2 mM palmitate and quantitatively collecting 14CO2 produced by the heart. In nonischemic hearts, 1 mM dichloroacetate increased steady-state glucose oxidation rates from 298 +/- 69 to 1,223 +/- 135 nmol.g dry wt-1.min-1. The addition of dichloroacetate to hearts reperfused after a 25-min period of ischemia also increased glucose oxidation rates from (112 +/- 25 to 561 +/- 83 nmol.g dry wt-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Isoflurane Alters Energy Substrate Metabolism to Preserve Mechanical Function in Isolated Rat Hearts following Prolonged No-Flow Hypothermic Storage

2003 ◽  
Vol 98 (2) ◽  
pp. 379-386 ◽  
Author(s):  
Barry A. Finegan ◽  
Manoj Gandhi ◽  
Matthew R. Cohen ◽  
Donald Legatt ◽  
Alexander S. Clanachan
Keyword(s):  
Enhanced Recovery ◽  
Metabolic Effects ◽  
Mechanical Function ◽  
Cardioplegic Arrest ◽  
Channel Activation ◽  
Energy Substrate ◽  
Myocardial Glucose Metabolism ◽  
Substrate Metabolism ◽  
Rat Hearts

Background Isoflurane enhances mechanical function in hearts subject to normothermic global or regional ischemia. The authors examined the effectiveness of isoflurane in preserving mechanical function in hearts subjected to cardioplegic arrest and prolonged hypothermic no-flow storage. The role of isoflurane in altering myocardial glucose metabolism during storage and reperfusion during these conditions and the contribution of adenosine triphosphate-sensitive potassium (K(atp)) channel activation in mediating the functional and metabolic effects of isoflurane preconditioning was determined. Methods Isolated working rat hearts were subjected to cardioplegic arrest with St. Thomas' II solution, hypothermic no-flow storage for 8 h, and subsequent aerobic reperfusion. The consequences of isoflurane treatment were assessed during the following conditions: (1) isoflurane exposure before and during storage; (2) brief isoflurane exposure during early nonworking poststorage reperfusion; and (3) isoflurane preconditioning before storage. The selective mitochondrial and sarcolemmal K(atp) channel antagonists, 5-hydroxydecanoate and HMR 1098, respectively, were used to assess the role of K(atp) channel activation on glycogen consumption during storage in isoflurane-preconditioned hearts. Results Isoflurane enhanced recovery of mechanical function if present before and during storage. Isoflurane preconditioning was also protective. Isoflurane reduced glycogen consumption during storage under the aforementioned circumstances. Storage of isoflurane-preconditioned hearts in the presence of 5-hydroxydecanoate prevented the reduction in glycogen consumption during storage and abolished the beneficial effect of isoflurane preconditioning on recovery of mechanical function. Conclusions Isoflurane provides additive protection of hearts subject to cardioplegic arrest and prolonged hypothermic no-flow storage and favorably alters energy substrate metabolism by modulating glycolysis during ischemia. The effects of isoflurane preconditioning on glycolysis during hypothermic no-flow storage appears to be associated with activation of mitochondrial K(atp) channels.

Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo

2012 ◽  
Vol 302 (4) ◽  
pp. E403-E408 ◽  
Author(s):  
Mika Bando ◽  
Hiroshi Iwakura ◽  
Hiroyuki Ariyasu ◽  
Hiroshi Hosoda ◽  
Go Yamada ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Medium Chain Triglyceride ◽  
Physiological Role ◽  
Standard Diet ◽  
Entry Site ◽  
Insulin Secretion In Vivo

Whereas ghrelin is produced primarily in the stomach, a small amount of it is produced in pancreatic islets. Although exogenous administration of ghrelin suppresses insulin secretion in vitro or in vivo, the role of intraislet ghrelin in the regulation of insulin secretion in vivo remains unclear. To understand the physiological role of intraislet ghrelin in insulin secretion and glucose metabolism, we developed a transgenic (Tg) mouse model, rat insulin II promoter ghrelin-internal ribosomal entry site-ghrelin O-acyl transferase (RIP-GG) Tg mice, in which mouse ghrelin cDNA and ghrelin O-acyltransferase are overexpressed under the control of the rat insulin II promoter. Although pancreatic desacyl ghrelin levels were elevated in RIP-GG Tg mice, pancreatic ghrelin levels were not altered in animals on a standard diet. However, when Tg mice were fed a medium-chain triglyceride-rich diet (MCTD), pancreatic ghrelin levels were elevated to ∼16 times that seen in control animals. It seems likely that the gastric ghrelin cells possess specific machinery to provide the octanoyl acid necessary for ghrelin acylation but that this machinery is absent from pancreatic β-cells. Despite the overexpression of ghrelin, plasma ghrelin levels in the portal veins of RIP-GG Tg mice were unchanged from control levels. Glucose tolerance, insulin secretion, and islet architecture in RIP-GG Tg mice were not significantly different even when the mice were fed a MCTD. These results indicate that intraislet ghrelin does not play a major role in the regulation of insulin secretion in vivo.

Glucose metabolism in rat hypothalamus

1981 ◽  
Vol 98 (4) ◽  
pp. 481-487 ◽  
Author(s):  
Pentti Lautala ◽  
Julio M. Martin
Keyword(s):  
Glucose Metabolism ◽  
Glucose Transport ◽  
Glucose Concentration ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Rat Hypothalamus ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
Phenazine Methosulphate

Abstract. In vitro glucose oxidation and glucose transport in the rat medial (MH) and lateral (LH) hypothalamic areas was measured. Glucose oxidation was calculated from the conversion of [U-14C]glucose to 14C02 and glucose transport from 14C02 produced from [114C]glucose in the presence of phenazine methosulphate and NaF. Increasing glucose in the medium from 1 him to 20 mm enhanced glucose oxidation two-fold in MH and 40% in LH. Addition of insulin, 100 (iU/ml, to the medium decreased glucose oxidation 30% both in MH and LH at both 4 mm and 20 mm glucose. Fasting did not affect glucose oxidation in either of these hypothalamic areas. Glucose transport was not affected by insulin, but was increased significantly when glucose was raised from 0.25 mm to 1.0 mm. Fasting also increased glucose transport in both hypothalamic areas. In conclusion, extracellular glucose concentration seems to be the major regulator of glucose utilization by the rat hypothalamus. Insulin, rather than increasing, seems to decrease glucose oxidation while having no effect on glucose transport.

scholarly journals Functional properties of edible insects: a systematic review

2021 ◽  
pp. 1-54
Author(s):  
V. D’Antonio ◽  
N. Battista ◽  
G. Sacchetti ◽  
C. Di Mattia ◽  
M. Serafini
Keyword(s):  
Glucose Metabolism ◽  
Functional Role ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
Edible Insects ◽  
Cellular Models ◽  
Pubmed Database

Abstract Consumption of edible insects has been widely suggested as an environmentally sustainable substitute for meat to reduce GHG emissions. However, the novel research field for edible insects rely on the content of bioactive ingredients and on the ability to induce a functional effect in humans. The goal of this manuscript was to review the available body of evidence on the properties of edible insects in modulating oxidative and inflammatory stress, platelet aggregation, lipid and glucose metabolism and weight control. A search for literature investigating the functional role of edible insects was carried out in the PUBMED database using specific keywords. A total of 55 studies, meeting inclusion criteria after screening, were divided on the basis of the experimental approach: in vitro studies, cellular models/ex vivo studies or in vivo studies. In the majority of the studies, insects demonstrated the ability to reduce oxidative stress, modulate antioxidant status, restore the impaired activity of antioxidant enzymes and reduce markers of oxidative damage. Edible insects displayed anti-inflammatory activity reducing cytokines and modulating specific transcription factors. Results from animal studies suggest that edible insects can modulate lipid and glucose metabolism. The limited number of studies focused on the assessment of anticoagulation activity of edible insects make it difficult to draw conclusions. More evidence from dietary intervention studies in humans is needed to support the promising evidence from in vitro and animal models about the functional role of edible insects consumption.

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