scholarly journals “A feed-forward Ca2+-dependent mechanism boosting glycolysis and OXPHOS by activating Aralar-malate-aspartate shuttle, upon neuronal stimulation”

2021 ◽  
Author(s):  
Irene Pérez-Liébana ◽  
Inés Juaristi ◽  
Paloma González-Sánchez ◽  
Luis González-Moreno ◽  
Eduardo Rial ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Cortical Neurons ◽  
Ryanodine Receptors ◽  
Lactate Production ◽  
Neuronal Activation ◽  
Respiratory Response ◽  
Neuronal Stimulation ◽  
Dependent Pathway ◽  
Malate Aspartate Shuttle ◽  
Dependent Mechanism

SummaryCalcium is an important second messenger regulating a bioenergetic response to the workloads triggered by neuronal activation. In cortical neurons using glucose as only fuel, activation by NMDA, which elicits a strong workload dependent on Na+ entry, stimulates glucose uptake, glycolysis, pyruvate and lactate production, and OXPHOS in a Ca2+-dependent way. We find that Ca2+-upregulation of glycolysis, pyruvate levels and respiration, but not glucose uptake, all depend on Aralar/AGC1/Slc25a12, the Ca2+regulated mitochondrial aspartate-glutamate carrier, component of the malate-aspartate shuttle (MAS). Ca2+-activation of MAS increases pyruvate production, which directly fuels workload-stimulated respiration. Also it stimulates glycolysis. MCU silencing had no effect indicating that none of these processes required mitochondrial Ca2+. The neuronal respiratory response to carbachol was also dependent on Aralar, but not on MCU. We also find that cortical neurons are endowed with a constitutive ER-to-mitochondria Ca2+ flow maintaining basal cell bioenergetics in which Ryanodine receptors, RyR2, rather than InsP3R, are responsible for Ca2+ release, and in which MCU does not participate. The results reveal that in neurons using glucose MCU does not participate in OXPHOS regulation under basal or stimulated conditions, while Aralar-MAS appears as the major Ca2+-dependent pathway tuning simultaneously glycolysis and OXPHOS to neuronal activation.

scholarly journals Chronically increased glucose uptake by adipose tissue leads to lactate production and improved insulin sensitivity rather than obesity in the mouse

Diabetologia ◽  
2010 ◽  
Vol 53 (11) ◽  
pp. 2417-2430 ◽  
Author(s):  
S. Muñoz ◽  
S. Franckhauser ◽  
I. Elias ◽  
T. Ferré ◽  
A. Hidalgo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Lactate Production

scholarly journals Leukemia inhibitory factor stimulates muscle glucose uptake by a PI3‐kinase dependent pathway that is maintained in white muscle in obesity (1162.4)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Nina Brandt ◽  
Hayley O'Neill ◽  
Maximilian Kleinert ◽  
Peter Schjerling ◽  
Gregory Steinberg ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Leukemia Inhibitory Factor ◽  
White Muscle ◽  
Pi3 Kinase ◽  
Inhibitory Factor ◽  
Dependent Pathway

scholarly journals α-Hederin Inhibits the Growth of Lung Cancer A549 Cells in vitro and in vivo by Increasing SIRT6 Dependent Glycolysis

2020 ◽  
Author(s):  
cong fang ◽  
Yahui Liu ◽  
Lanying Chen ◽  
Yingying Luo ◽  
Yaru Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Protein Expression ◽  
Glucose Uptake ◽  
A549 Cells ◽  
Lactate Production ◽  
Tumor Xenograft ◽  
Xenograft Mouse Model ◽  
Atp Generation

Abstract Background: α-hederin an effective component of Pulsatilla chinensis (Bunge) Regel, Studies showed that α-hederin exert many pharmacological activities, However, the effect of α-hederin on metabolism is still unclear. This study aimed to illuminate the role of α-hederin in glucose metabolism in lung cancer cells and investigate the molecular mechanism of α-hederin. Methods: CCK8 and colony formation assays were employed to assess the anti-proliferative effects induced by α-hederin. Glucose uptake, ATP generation, and reduced lactate production were measured using kits, and an A549 tumor xenograft mouse model of lung cancer was used to assess the in vivo antitumor effect of α-hederin (5, 10 mg/kg). Glycolytic-related key enzymes hexokinase 2 (HK2), glucose transporters 1 (GLUT1), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), monocarboxylate transporter (MCT4), c-Myc, Hypoxia inducible factor-1α (HIF-1α) and Sirtuin 6 (SIRT6) protein expression were detected by western blotting and immunohistochemical staining and SIRT6 inhibitors was verified in A549 cells. Results: Our results showed that cell proliferation was significantly inhibited by α-hederin in a dose-dependent manner and that α-hederin inhibited glucose uptake and ATP generation and reduced lactate production. Furthermore, α-hederin remarkably inhibited HK2, GLUT1, PKM2, LDHA, MCT4, c-Myc, HIF-1α and activated SIRT6 protein expression. Using inhibitors, we proved that α-hederin inhibits glycolysis by activating SIRT6. Moreover, a tumor xenograft mouse model of lung cancer further confirmed that α-hederin inhibits lung cancer growth via inhibiting glycolysis in vivo. Conclusions: α-hederin inhibits the growth of non-small cell lung cancer A549 cells by inhibiting glycolysis. The mechanism of glycolysis inhibition includes α-hederin activating the expression of the glycolytic related protein SIRT6.

scholarly journals Human TNF-α Affects the Egg-laying Dynamics and Glucose Metabolism of Schistosoma Mansoni Adult Worms in Vitro

2021 ◽  
Author(s):  
Ednilson Hilário Lopes-Junior ◽  
Gilbert de Oliveira Silveira ◽  
Camila Banca Guedes ◽  
Gratchela Dutra Rodrigues ◽  
Viviane Sousa Ribeiro ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Mrna Expression ◽  
Glucose Uptake ◽  
Lactate Production ◽  
Egg Laying ◽  
Dependent Manner ◽  
Tnf Α ◽  
Atp Metabolism ◽  
Fine Regulation

Abstract Several studies described the effect of human TNF-α on Schistosoma mansoni. It affects the worm’s development, metabolism, egg-laying, changes in the parasite´s gene expression and protein phosphorylation. Data available concerning the influence of hTNF-α on egg-laying are controversial and understanding the mechanism of egg-laying regulation is essential in combating schistosomiasis. We characterized the effects of in vitro treatment of S. mansoni adult worms with different doses of hTNF-α (5, 20 and 40ng/mL) for five days. We explored the effects on the egg-laying rate, glucose, ATP metabolism, mRNA expression levels of lactate dehydrogenase, of glucose transporters and of SmTNFR, the parasite gene for hTNF-α receptor. hTNF-α influenced egg-laying in a time and dose dependent manner: with 40ng/mL, egg-laying increased on day 2 and decreased on days 3 and 4; 20 ng/mL dose, egg-laying decreased on day 3, while at 5ng/mL dose, egg-laying decreased on day 4. The total number of eggs produced was not affected, but the egg-laying dynamic was altered; the median egg-laying time decreased significantly due to treatment. At 5 and 20ng/mL hTNF-alpha, lactate production diminished on days 3 up to 5, while glucose uptake increased on day 5. At 40ng/mL, glucose uptake diminished on days 1 up to 3, while ATP accumulation was detected on day 5. No significant changes in the mRNA expression were detected in all treatments. Crosstalk involving the hTNF-alpha and the parasite signaling play a role in the fine regulation of the worm´s metabolism and physiology and points to new strategies for disease control.

scholarly journals Oligodendrocytes contribute to motor neuron death in ALS via SOD1-dependent mechanism

2016 ◽  
Vol 113 (42) ◽  
pp. E6496-E6505 ◽  
Author(s):  
Laura Ferraiuolo ◽  
Kathrin Meyer ◽  
Thomas W. Sherwood ◽  
Jonathan Vick ◽  
Shibi Likhite ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Lactate Production ◽  
Chromosome 9 ◽  
Neuron Death ◽  
Motor Neuron Death ◽  
Repeat Expansions ◽  
Human Oligodendrocytes ◽  
Lateral Sclerosis ◽  
Dependent Mechanism

Oligodendrocytes have recently been implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). Here we show that, in vitro, mutant superoxide dismutase 1 (SOD1) mouse oligodendrocytes induce WT motor neuron (MN) hyperexcitability and death. Moreover, we efficiently derived human oligodendrocytes from a large number of controls and patients with sporadic and familial ALS, using two different reprogramming methods. All ALS oligodendrocyte lines induced MN death through conditioned medium (CM) and in coculture. CM-mediated MN death was associated with decreased lactate production and release, whereas toxicity in coculture was lactate-independent, demonstrating that MN survival is mediated not only by soluble factors. Remarkably, human SOD1 shRNA treatment resulted in MN rescue in both mouse and human cultures when knockdown was achieved in progenitor cells, whereas it was ineffective in differentiated oligodendrocytes. In fact, early SOD1 knockdown rescued lactate impairment and cell toxicity in all lines tested, with the exclusion of samples carrying chromosome 9 ORF 72 (C9orf72) repeat expansions. These did not respond to SOD1 knockdown nor did they show lactate release impairment. Our data indicate that SOD1 is directly or indirectly involved in ALS oligodendrocyte pathology and suggest that in this cell type, some damage might be irreversible. In addition, we demonstrate that patients with C9ORF72 represent an independent patient group that might not respond to the same treatment.

Kaempferol Promotes Glucose Uptake in Myotubes through a JAK2-Dependent Pathway

2020 ◽  
Vol 68 (47) ◽  
pp. 13720-13729
Author(s):  
Tomoya Kitakaze ◽  
Hao Jiang ◽  
Takuya Nomura ◽  
Ken-yu Hironao ◽  
Yoko Yamashita ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Dependent Pathway

Effects of insulin on glucose uptake by rat hearts during and after coronary flow reduction

1997 ◽  
Vol 273 (5) ◽  
pp. H2170-H2177 ◽  
Author(s):  
T. Minsue Chen ◽  
Gary W. Goodwin ◽  
Patrick H. Guthrie ◽  
Heinrich Taegtmeyer
Keyword(s):  
Glucose Uptake ◽  
Intracellular Signaling ◽  
Glycogen Synthesis ◽  
Lactate Production ◽  
Low Flow ◽  
Rat Hearts ◽  
Ischemic Period ◽  
Postischemic Period ◽  
Insulin Responsiveness ◽  
Fasted Rats

We tested the hypothesis that low-flow ischemia increases glucose uptake and reduces insulin responsiveness. Working hearts from fasted rats were perfused with buffer containing glucose alone or glucose plus a second substrate (lactate, octanoate, or β-hydroxybutyrate). Rates of glucose uptake were measured by3H2O production from [2-3H]glucose. After 15 min of perfusion at a physiological workload, hearts were subjected to low-flow ischemia for 45 min, after which they were returned to control conditions for another 30 min. Insulin (1 mU/ml) was added before, during, or after the ischemic period. Cardiac power decreased by 70% with ischemia and returned to preischemic values on reperfusion in all groups. Low-flow ischemia increased lactate production, but the rate of glucose uptake during ischemia increased only when a second substrate was present. Hearts remained insulin responsive under all conditions. Insulin doubled glucose uptake when added under control conditions, during low-flow ischemia, and at the onset of the postischemic period. Insulin also increased net glycogen synthesis in postischemic hearts perfused with glucose and a second substrate. Thus insulin stimulates glucose uptake in normal and ischemic hearts of fasted rats, whereas ischemia stimulates glucose uptake only in the presence of a cosubstrate. The results are consistent with two separate intracellular signaling pathways for hexose transport, one that is sensitive to the metabolic requirements of the heart and another that is sensitive to insulin.

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