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Insulin regulates alveolar epithelial function by inducing Na+/K+-ATPase translocation to the plasma membrane in a process mediated by the action of Akt.
- Source :
-
Journal of cell science [J Cell Sci] 2010 Apr 15; Vol. 123 (Pt 8), pp. 1343-51. Date of Electronic Publication: 2010 Mar 23. - Publication Year :
- 2010
-
Abstract
- Stimulation of Na(+)/K(+)-ATPase translocation to the cell surface increases active Na(+) transport, which is the driving force of alveolar fluid reabsorption, a process necessary to keep the lungs free of edema and to allow normal gas exchange. Here, we provide evidence that insulin increases alveolar fluid reabsorption and Na(+)/K(+)-ATPase activity by increasing its translocation to the plasma membrane in alveolar epithelial cells. Insulin-induced Akt activation is necessary and sufficient to promote Na(+)/K(+)-ATPase translocation to the plasma membrane. Phosphorylation of AS160 by Akt is also required in this process, whereas inactivation of the Rab GTPase-activating protein domain of AS160 promotes partial Na(+)/K(+)-ATPase translocation in the absence of insulin. We found that Rab10 functions as a downstream target of AS160 in insulin-induced Na(+)/K(+)-ATPase translocation. Collectively, these results suggest that Akt plays a major role in Na(+)/K(+)-ATPase intracellular translocation and thus in alveolar fluid reabsorption.
- Subjects :
- Animals
Body Fluids drug effects
Body Fluids enzymology
Cattle
GTPase-Activating Proteins metabolism
Humans
Male
Phosphatidylinositol 3-Kinases metabolism
Protein Transport drug effects
Rats
Rats, Sprague-Dawley
Subcellular Fractions drug effects
Subcellular Fractions enzymology
rab GTP-Binding Proteins metabolism
Alveolar Epithelial Cells drug effects
Alveolar Epithelial Cells enzymology
Cell Membrane drug effects
Cell Membrane enzymology
Insulin pharmacology
Proto-Oncogene Proteins c-akt metabolism
Sodium-Potassium-Exchanging ATPase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1477-9137
- Volume :
- 123
- Issue :
- Pt 8
- Database :
- MEDLINE
- Journal :
- Journal of cell science
- Publication Type :
- Academic Journal
- Accession number :
- 20332111
- Full Text :
- https://doi.org/10.1242/jcs.066464