THE ROLE AND REGULATION OF PHOSPHOLIPASE D IN BRAIN INSULIN SIGNALING PATHWAY
N.A. Babenko, V.S. Kharchenko
Research Institute of Biology of the V. N. Karazin Kharkiv National University, Kharkiv, Ukraine
DOI: https://doi.org/10.15407/fz64.02.040
Abstract
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
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