Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D
Joint Authors
Babenko, Nataliya A.
Kharchenko, Vitalina S.
Source
International Journal of Endocrinology
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-05-24
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Background.
The role of phospholipase D (PLD) as a positive modulator of glucose uptake activation by insulin in muscle and adipose cells has been demonstrated.
The role of PLD in the regulation of glucose metabolism by insulin in the primary hepatocytes has been determined in this study.
Methods.
For this purpose, we studied effects of inhibitors of PLD on glucose uptake and glycogen synthesis stimulation by insulin.
To determine the PLD activity, the method based on determination of products of transphosphatidylation reaction, phosphatidylethanol or phosphatidylbutanol, was used.
Results.
Inhibition of PLD by a general antagonist (1-butanol) or specific inhibitor, halopemide, or N-hexanoylsphingosine, or by cellular ceramides accumulated in doxorubicin-treated hepatocytes decreased insulin-stimulated glucose metabolism.
Doxorubicin-induced hepatocytes resistance to insulin action could be abolished by inhibition of ceramide production.
Halopemide could nullify this effect.
Addition of propranolol, as well as inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) (wortmannin, LY294002) or suppressors of Akt phosphorylation/activity, luteolin-7-O-glucoside or apigenin-7-O-glucoside, to the culture media could block cell response to insulin action.
Conclusion.
PLD plays an important role in the insulin signaling in the hepatocytes.
PLD is activated downstream of PI3-kinase and Akt and is highly sensitive to ceramide content in the liver cells.
American Psychological Association (APA)
Babenko, Nataliya A.& Kharchenko, Vitalina S.. 2015. Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D. International Journal of Endocrinology،Vol. 2015, no. 2015, pp.1-15.
https://search.emarefa.net/detail/BIM-1065814
Modern Language Association (MLA)
Babenko, Nataliya A.& Kharchenko, Vitalina S.. Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D. International Journal of Endocrinology No. 2015 (2015), pp.1-15.
https://search.emarefa.net/detail/BIM-1065814
American Medical Association (AMA)
Babenko, Nataliya A.& Kharchenko, Vitalina S.. Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D. International Journal of Endocrinology. 2015. Vol. 2015, no. 2015, pp.1-15.
https://search.emarefa.net/detail/BIM-1065814
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1065814