Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2018; 64(2): 40-46


N.A. Babenko, V.S. Kharchenko

    Research Institute of Biology of the V. N. Karazin Kharkiv National University, Kharkiv, Ukraine


The role of phospholipase D as a positive modulator of glucose uptake activation by insulin in the neocortex of 3-month-old rats were studied by using specific inhibitors of signaling pathways of insulin (wortmannin, LY294002, halopemide, C6-ceramide). It was found that in the rat neocortex inhibitors decreased the insulin-induced accumulation of phosphatidylethanol from 163% in the control to 115% under the influence of wortmannin and 112% under the action of LY294002. Inhibition of insulin stimulated phospholipase D by phosphatidylinositol-3-kinase inhibitors (wortmannin and LY294002) indicated downstream regulation of phospholipase D by phosphatidylinositol-3- kinase. The suppression of this phospholipase by a specific inhibitor haloperimide is accompanied by a decrease in the amount of labeled glucose in the neocortical tissue from 154% in the control to 111% under the influence of the inhibitor. Inhibition of insulin-induced glucose uptake by specific inhibitor of phospholipase D halopemide points to the key role of the enzyme in the regulation of glucose uptake in the rat neocortex. In addition, phospholipase D-dependent insulin signaling and glucose uptake in the rat cerebral cortex are highly sensitive to intracellular ceramide content. The results obtained in this study provide that modulation of PLD activity, as well as ceramides content in the cells, can be a useful tool for manipulating the nerve tissue sensitivity to insulin action

Keywords: phosphatidylinositol-3-kinase; phospholipase D; insulin; ceramide; neocortex; rats


  1. Kanaho Y, Funakoshi Y, Hasegawa H. Phospholipase D signalling and its involvement in neurite outgrowth. Biochim Biophys Acta. 2009; 1791(9):898-904. CrossRef PubMed
  3. Rankovic M, Jacob L, Rankovic V, Brandenburg LO, Schröder H, Höllt V, et al. ADP-ribosylation factor 6 regulates mu-opioid receptor trafficking and signaling via activation of phospholipase D2. Cell Signal. 2009; 21(12):1784-93. CrossRef PubMed
  5. Lee HC, Fellenz-Maloney MP, Liscovitch M, Blusztajn JK. Phospholipase D-catalyzed hydrolysis of phosphatidylcholine provides the choline precursor for acetylcholine synthesis in a human neuronal cell line. Proc Natl Acad Sci U S A. 1993; 90(21):10086-90. CrossRef PubMed PubMedCentral
  7. Salvador GA, Ilincheta de Boschero MG, Pasquaré SJ, Giusto NM. Phosphatidic acid and diacylglycerol generation is regulated by insulin in cerebral cortex synaptosomes from adult and aged rats. J Neurosci Res. 2005; 81(2):244-52. CrossRef PubMed
  9. Laron Z. Insulin and the brain. Arch Physiol Biochem. 2009; 115(2):112-6. CrossRef PubMed
  11. Bak LK, Schousboe A, Sonnewald U, Waagepetersen HS. Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. J Cereb Blood Flow Metab. 2006; 26(10):1285-97. CrossRef PubMed
  13. Bak LK, Walls AB, Schousboe A, Ring A, Sonnewald U, Waagepetersen HS. Neuronal glucose but not lactate utilization is positively correlated with NMDA-induced neurotransmission and fluctuations in cytosolic Ca2+ levels. J Neurochem. 2009; 109 Suppl 1:87-93. CrossRef PubMed
  15. Winocur G, Greenwood CE, Piroli GG, Grillo CA, Reznikov LR, Reagan LP, et al. Memory impairment in obese Zucker rats: an investigation of cognitive function in an animal model of insulin resistance and obesity. Behav Neurosci. 2005; 119(5):1389-95. CrossRef PubMed
  17. Xu Y, Rubin BR, Orme CM, Karpikov A, Yu C, Bogan JS, Toomre DK. Dual-mode of insulin action controls GLUT4 vesicle exocytosis. J Cell Biol. 2011; 193(4):643-53. CrossRef PubMed PubMedCentral
  19. Huang P, Altshuller YM, Hou JC, Pessin JE, Frohman MA. Insulin-stimulated plasma membrane fusion of Glut4 glucose transporter-containing vesicles is regulated by phospholipase D1. Mol Biol Cell. 2005; 16(6):2614-23. CrossRef PubMed PubMedCentral
  21. Babenko NA, Kharchenko VS. Modulation of insulin sensitivity of hepatocytes by the pharmacological downregulation of phospholipase D. Int J Endocrin. 2015; 794838. PubMed PubMedCentral
  23. Mokrushin AA, Pavlinova L I. Effects of the blood components on the AMPA and NMDA synaptic responses in brain slices in the onset of hemorrhagic stroke. Gen Physiol Biophys. 2013; 32: 489-504. CrossRef PubMed
  25. Oliveira TG, Di Paolo G. Phospholipase D in brain function and Alzheimer's disease. Biochim Biophys Acta. 2010; 1801(8):799-805. CrossRef PubMed PubMedCentral
  27. Heni M, Hennige AM, Peter A, Siegel-Axel D, Ordelheide AM, Krebs N, et al. Insulin promotes glycogen storage and cell proliferation in primary human astrocytes. PLoS ONE. 2011; 6(6): e21594. CrossRef PubMed PubMedCentral
  29. Lowry ON, Rosebrough NJ, Farr AL, Randal RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951; 193:365-75.
  31. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959; 37(8):911-17. CrossRef PubMed
  33. Babenko NA, Kharchenko VS. Effects of aging and experimentaly induced signal pathway modifications on insulin-induced changes of glucose metabolism in rat cerebral cortex. Neurophysiol. 2015; 47(1):16-22. CrossRef  
  34. Hasselbalch SG, Knudsen GM, Videbaek C, Pinborg LH, Schmidt JF, Holm S, et al. No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans. Diabetes. 1999; 48(10):1915-21. CrossRef PubMed
  36. Doré S, Kar S, Rowe W, Quirion R. Distribution and levels of [125I]IGF-I, [125I]IGF-II and [125I]insulin receptor binding sites in the hippocampus of aged memory-unimpaired and impaired rats. Neuroscience. 1997; 80(4):1033-40. CrossRef  
  37. McEwen BS, Reagan LP. Glucose transporter expression in the central nervous system: relationship to synaptic function. Eur J Pharmacol. 2004; 490(1-3):13-24. CrossRef PubMed
  39. Jacques-Silva MC, Bernardi A, Rodnight R, Lenz G. ERK, PKC and PI3K/Akt pathways mediate extracellular ATP and adenosine-induced proliferation of U138-MG human glioma cell line. Oncology. 2004;67(5-6):450-9. CrossRef PubMed
  41. Sun SH, Lin LB, Hung AC, Kuo JS. ATP-stimulated Ca2+ influx and phospholipase D activities of a rat brain-derived type-2 astrocyte cell line, RBA-2, are mediated through P2X7 receptors. J Neurochem. 1999; 73(1):334-43. CrossRef PubMed
  43. Selvy PE, Lavieri RR, Lindsley CW, Brown HA. Phospholipase D: enzymology, functionality, and chemical modulation. Chem Rev. 2011; 111(10):6064-119. CrossRef PubMed PubMedCentral
  45. Bourbon NA, Sandirasegarane L, Kester M. Ceramideinduced inhibition of Akt is mediated through protein kinase Czeta: implications for growth arrest. J Biol Chem. 2002; 277(5):3286-92. CrossRef PubMed
  47. Pasquaré SJ, Gaveglio VL, Giusto NM. Regulation of phosphatidic Acid metabolism by sphingolipids in the central nervous system. J Lipids. 2011; 2011:342576. CrossRef PubMed PubMedCentral
  49. Nakashima S, Nozawa Y. Possible role of phospholipase D in cellular differentiation and apoptosis. Chem Phys Lipids. 1999; 98(1-2):153-64. CrossRef  

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.