scholarly journals Role of fructose 2,6-bisphosphate in the stimulation of glycolysis by anoxia in isolated hepatocytes

1982 ◽  
Vol 206 (2) ◽  
pp. 359-365 ◽  
Author(s):  
L Hue
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Amp ◽  
Adenine Nucleotides ◽  
Lactate Production ◽  
Isolated Hepatocytes ◽  
Anaerobic Glycolysis ◽  
Anaerobic Conditions ◽  
Effect Of Glucose ◽  
Stimulation Of

1. Incubation of hepatocytes from fed or starved rats with increasing glucose concentrations caused a stimulation of lactate production, which was further increased under anaerobic conditions. 2. When glycolysis was stimulated by anoxia, [fructose 2,6-bis-phosphate] was decreased, indicating that this ester could not be responsible for the onset of anaerobic glycolysis. In addition, the effect of glucose in increasing [fructose 2,6-bisphosphate] under aerobic conditions was greatly impaired in anoxic hepatocytes. [Fructose 2,6-bisphosphate] was also diminished in ischaemic liver, skeletal muscle and heart. 3. The following changes in metabolite concentration were observed in anaerobic hepatocytes: AMP, ADP, lactate and L-glycerol 3-phosphate were increased; ATP, citrate and pyruvate were decreased: phosphoenolpyruvate and hexose 6-phosphates were little affected. Concentrations of adenine nucleotides were, however, little changed by anoxia when hepatocytes from fed rats were incubated with 50 mM-glucose. 4. The activity of ATP:fructose 6-phosphate 2-phosphotransferase was not affected by anoxia but decreased by cyclic AMP. 5. The role of fructose 2,6-bisphosphate in the regulation of glycolysis is discussed.

Adenosine protects ischemic and reperfused myocardium by receptor-mediated mechanisms

1993 ◽  
Vol 264 (1) ◽  
pp. H163-H170 ◽  
Author(s):  
M. F. Janier ◽  
J. L. Vanoverschelde ◽  
S. R. Bergmann
Keyword(s):  
Protective Action ◽  
Lactate Production ◽  
Low Flow ◽  
Anaerobic Glycolysis ◽  
Ischemia And Reperfusion ◽  
Tissue Necrosis ◽  
Ischemic Contracture ◽  
Developed Pressure ◽  
Stimulation Of

To evaluate the role of adenosine receptors in the mediation of adenosine-induced protection of the heart during ischemia and reperfusion, isolated rabbit hearts were perfused at constant flow with 1 microM adenosine started before low-flow ischemia followed by reperfusion. Adenosine delayed the time of onset of ischemic contracture [to 28 +/- 19 (SD) min compared with 10 +/- 10 min in control hearts] and decreased the amplitude of ischemic contracture (29 +/- 16 vs. 48 +/- 14 mmHg; P<0.05 for each compared with controls). This protection was accompanied by an increase in tissue ATP content (1.72 +/- 0.78 vs. 0.96 +/- 0.23 mumol/g; P < 0.05) and stimulation of anaerobic glycolysis (lactate production of 0.78 +/- 0.28 mumol.g-1 x min-1 compared with 0.53 +/- 0.23 mumol.g-1 x min-1; P < 0.05). Functional recovery during reperfusion was enhanced by adenosine (developed pressure 88 +/- 16% compared with 57 +/- 23% of baseline; P < 0.05), and tissue necrosis, assessed by creatine kinase release, was decreased. The potent, nonselective adenosine receptor blocker 8-phenyltheophylline (10 microM) blocked all of the salutary effects of adenosine. Adenosine given only at reperfusion modestly attenuated reperfusion-induced contracture. The results suggest that exogenous adenosine attenuates ischemic injury by receptor-mediated stimulation of anaerobic glycolysis. During reperfusion its protective action is related to vasodilation.

scholarly journals Unappreciated Role of LDHA and LDHB to Control Apoptosis and Autophagy in Tumor Cells

2019 ◽  
Vol 20 (9) ◽  
pp. 2085 ◽  
Author(s):  
Kaja Urbańska ◽  
Arkadiusz Orzechowski
Keyword(s):  
Lactate Dehydrogenase ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Lactate Production ◽  
Anaerobic Glycolysis ◽  
Anaerobic Conditions ◽  
Metabolic Plasticity ◽  
Made In

Tumor cells possess a high metabolic plasticity, which drives them to switch on the anaerobic glycolysis and lactate production when challenged by hypoxia. Among the enzymes mediating this plasticity through bidirectional conversion of pyruvate and lactate, the lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB), are indicated. LDHA has a higher affinity for pyruvate, preferentially converting pyruvate to lactate, and NADH to NAD+ in anaerobic conditions, whereas LDHB possess a higher affinity for lactate, preferentially converting lactate to pyruvate, and NAD+ to NADH, when oxygen is abundant. Apart from the undisputed role of LDHA and LDHB in tumor cell metabolism and adaptation to unfavorable environmental or cellular conditions, these enzymes participate in the regulation of cell death. This review presents the latest progress made in this area on the roles of LDHA and LDHB in apoptosis and autophagy of tumor cells. Several examples of how LDHA and LDHB impact on these processes, as well as possible molecular mechanisms, will be discussed in this article. The information included in this review points to the legitimacy of modulating LDHA and/or LDHB to target tumor cells in the context of human and veterinary medicine.

Role of epinephrine during insulin-induced hypoglycemia in fasted rats

1994 ◽  
Vol 77 (1) ◽  
pp. 270-276 ◽  
Author(s):  
W. W. Winder ◽  
P. S. MacLean ◽  
S. L. Chandler ◽  
W. Huang ◽  
R. H. Mills
Keyword(s):  
Skeletal Muscle ◽  
Blood Glucose ◽  
Plasma Insulin ◽  
Insulin Infusion ◽  
Lactate Production ◽  
Plasma Epinephrine ◽  
Fasted Rats ◽  
Gluconeogenic Substrate ◽  
Stimulation Of

Responses to insulin-induced hypoglycemia in fasted sham-operated (SHAM), adrenodemedullated (ADM), and epinephrine-infused ADM (ADM + E) rats were studied to ascertain the specific role of epinephrine in increasing resting skeletal muscle content of adenosine 3′,5′-cyclic monophosphate (cAMP) and fructose 2,6-bisphosphate (F-2,6-P2), which are involved in stimulation of muscle glycogenolysis and lactate production. Rats from each group were fasted for 24 h and then infused intravenously with insulin (30, 60, or 90 min) to produce plasma insulin values of approximately 92 microU/ml. One-half of the insulin-infused ADM rats were also infused with epinephrine (ADM + E). Muscle and blood lactate, muscle cAMP, and muscle F-2,6-P2 increased and muscle glycogen decreased in SHAM rats. Each of these changes was prevented or attenuated in ADM rats and restored in ADM + E rats. Liver cAMP, glycogen, and F-2,6-P2 responses to hypoglycemia were similar in SHAM, ADM, and ADM + E rats. Blood glucose decreased to 0.74 +/- 0.05 mM in ADM rats compared with 1.54 +/- 0.11 mM in SHAM and 1.34 +/- 0.15 mM in ADM + E rats after 90 min of insulin infusion. The increase in plasma epinephrine is therefore essential in the counterregulatory response to insulin-induced hypoglycemia in fasted rats. Resting skeletal muscle glycogenolysis and lactate production for hepatic gluconeogenic substrate appear to be important components of the counterregulatory response in fasted rats.

Role of skeletal muscle Na+–K+ ATPase activity in increased lactate production in sub–acute sepsis

Life Sciences ◽  
2002 ◽  
Vol 70 (16) ◽  
pp. 1875-1888 ◽  
Author(s):  
Freda D McCarter ◽  
S.Renee Nierman ◽  
J.Howard James ◽  
Li Wang ◽  
Jy-Kung King ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Atpase Activity ◽  
Lactate Production

scholarly journals The role of insulin in the modulation of glucagon-dependent control of phenylalanine hydroxylation in isolated liver cells

1987 ◽  
Vol 242 (3) ◽  
pp. 655-660 ◽  
Author(s):  
M J Fisher ◽  
A J Dickson ◽  
C I Pogson
Keyword(s):  
Cyclic Amp ◽  
Insulin Action ◽  
Phenylalanine Hydroxylase ◽  
Liver Cells ◽  
Phosphorylation State ◽  
Isolated Liver Cells ◽  
The Impact ◽  
Isolated Liver ◽  
Stimulation Of

The stimulation of phenylalanine hydroxylation in isolated liver cells by sub-maximally effective concentrations of glucagon (less than 0.1 microM) is antagonized by insulin (0.1 nM-0.1 microM). This phenomenon is a consequence of a decrease in the glucagon-stimulated phosphorylation of phenylalanine hydroxylase from liver cells incubated in the presence of insulin. The impact of insulin on the phosphorylation state and activity of the hydroxylase is mimicked by incubation of liver cells in the presence of orthovanadate (10 microM). A series of cyclic AMP and cyclic GMP analogues enhanced phenylalanine hydroxylation: in each case insulin diminished the stimulation of flux. These results are discussed in the light of the characteristics of insulin action on other metabolic processes.

Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck

1979 ◽  
Vol 237 (5) ◽  
pp. C200-C204 ◽  
Author(s):  
D. J. Stewart ◽  
J. Sax ◽  
R. Funk ◽  
A. K. Sen
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Salt Gland ◽  
Domestic Ducks ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.

Mechanisms of Pi regulation of the skeletal muscle SR Ca2+ release channel

2000 ◽  
Vol 278 (3) ◽  
pp. C601-C611 ◽  
Author(s):  
Edward M. Balog ◽  
Bradley R. Fruen ◽  
Patricia K. Kane ◽  
Charles F. Louis
Keyword(s):  
Skeletal Muscle ◽  
Single Channel ◽  
Adenine Nucleotides ◽  
Muscle Fibers ◽  
Open Probability ◽  
Release Channel ◽  
High Concentrations ◽  
Channel Open Time ◽  
Stimulation Of

Inorganic phosphate (Pi) accumulates in the fibers of actively working muscle where it acts at various sites to modulate contraction. To characterize the role of Pi as a regulator of the sarcoplasmic reticulum (SR) calcium (Ca2+) release channel, we examined the action of Pi on purified SR Ca2+ release channels, isolated SR vesicles, and skinned skeletal muscle fibers. In single channel studies, addition of Pi to the cis chamber increased single channel open probability ( P o; 0.079 ± 0.020 in 0 Pi, 0.157 ± 0.034 in 20 mM Pi) by decreasing mean channel closed time; mean channel open times were unaffected. In contrast, the ATP analog, β,γ-methyleneadenosine 5′-triphosphate (AMP-PCP), enhanced P o by increasing single channel open time and decreasing channel closed time. Pi stimulation of [3H]ryanodine binding by SR vesicles was similar at all concentrations of AMP-PCP, suggesting Pi and adenine nucleotides act via independent sites. In skinned muscle fibers, 40 mM Pi enhanced Ca2+-induced Ca2+ release, suggesting an in situ stimulation of the release channel by high concentrations of Pi. Our results support the hypothesis that Pi may be an important endogenous modulator of the skeletal muscle SR Ca2+ release channel under fatiguing conditions in vivo, acting via a mechanism distinct from adenine nucleotides.

Metabolic requirements for anaerobic active Cl and Na transport in the bullfrog cornea

1979 ◽  
Vol 236 (5) ◽  
pp. C268-C276 ◽  
Author(s):  
P. S. Reinach ◽  
H. F. Schoen ◽  
O. A. Candia
Keyword(s):  
Energy Source ◽  
Amphotericin B ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Anaerobic Glycolysis ◽  
Anaerobic Conditions ◽  
Na Transport ◽  
Sufficient Energy ◽  
Aerobic And Anaerobic ◽  
Stimulation Of

In the bullfrog cornea, the relationships between the rates of aerobic and anaerobic glycolysis and active Cl and Na transport were studied. In NaCl Ringer (glucose-free), the short-circuit current (SCC) declined much more slowly under aerobic than under anaerobic conditions. The aerobic lactate effluxes in glucose-free and glucose-rich NaCl Ringer were 0.08 and 0.23 micromol/h.cm2, respectively. The transition to anoxia caused these values to increase significantly and was accompanied by depletion of endogenous glycogen in glucose-free Ringer. In Na2SO4 Ringer, amphotericin B (10(-5) M) stimulation of the aerobic SCC was not dependent on the presence of glucose but under anoxia, SCC stimulation required glucose. In Na2SO4 (glucose-rich) Ringer, amphotericin B stimulated the aerobic lactate efflux from 0.26 to 0.36 mumol/h.cm2 and anoxia increased it to 0.55 micromol/h.cm2. In NaCl Ringer, the addition of either 0.5 mM adenosine or 1 mM ATP with 26 mM glucose restored the anaerobic-inhibited SCC and lactate efflux of glucose-depleted corneas. The results show that the reactions of glycolysis are a sufficient energy source for supporting active Na and Cl transport.

Inhibitors such as staurosporine, H-7 or polymyxin B cannot be used in skeletal muscle to prove the role of protein kinase C on insulin action

1992 ◽  
Vol 12 (5) ◽  
pp. 413-424 ◽  
Author(s):  
Anna Gumà ◽  
Purificación Muñoz ◽  
Marta Camps ◽  
Xavier Testar ◽  
Manuel Palacín ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Insulin Action ◽  
Lactate Production ◽  
Polymyxin B ◽  
Transport Activity ◽  
System A ◽  
Kinase C

The precise role of protein kinase C in insulin action in skeletal muscle is not well defined. Based on the fact that inhibitors of protein kinase C block some insulin effects, it has been concluded that some of the biological actions of insulin are mediated via protein kinase C. In this study, we present evidence that inhibitors of protein kinase C such as staurosporine, H-7 or polymyxin B cannot be used to ascertain the role of protein kinase C in skeletal muscle. This is based on the following experimental evidences: a) staurosporine, H-7 and polymyxin B markedly block in muscle the effect of insulin on System A transport activity; however, this effect of insulin is not mimicked in muscle by TPA-induced stimulation of protein kinase C, b) H-7 and polymyxin B block insulin action on System A transport activity in an additive manner to the inhibitory effect of phorbol esters, c) staurosporine, H-7 and polymyxin B block the effect of insulin on lactate production, a process that is activated by insulin and TPA in an additive fashion, and d) staurosporine completely blocks the tyrosine kinase activity of insulin receptors partially purified from rat skeletal muscle.

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