Document Detail


Insulin increases the functional activity of the renal NaCl cotransporter.
MedLine Citation:
PMID:  23303355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Insulin is recognized to increase renal salt reabsorption in the distal nephron and hyperinsulinemic states have been shown to be associated with increased expression of the renal NaCl cotransporter (NCC). However, the effect of insulin on NCC functional activity has not been reported.
METHODS: Using a heterologous expression system of Xenopus laevis oocytes, a mouse distal convoluted cell line, mDCT15 cells, endogenously expressing NCC, and an ex-vivo kidney perfusion technique, we assessed the effect of insulin on the activity and phosphorylation of NCC. The signaling pathway involved was analyzed.
RESULTS: In Xenopus oocytes insulin increases the activity of NCC together with its phosphorylation at threonine residue 58. Activation of NCC by insulin was also observed in mDCT15 cells. Additionally, insulin increased the NCC phosphorylation in kidney under the ex-vivo perfusion technique. In oocytes and mDCT15 cells, insulin effect on NCC was prevented with inhibitors of phosphatidylinositol 3-kinase (PI3K), mTORC2, and AKT1 kinases, but not by inhibitors of MAP or mTORC1 kinases, suggesting that PI3K-mTORC2-AKT1 is the intracellular pathway required. Additionally, activation of NCC by insulin was not affected by wild-type or mutant versions of with no lysine kinase 1, with no lysine kinase 4, or serum glucocorticoid kinase 1, but it was no longer observed in the presence of wild-type or the dominant negative, catalytically inactive with no lysine kinase 3, implicating this kinase in the process.
CONCLUSION: Insulin induces activation and phosphorylation of NCC. This effect could play an important role in arterial hypertension associated with hyperinsulinemic states, such as obesity, metabolic syndrome, or type 2 diabetes mellitus.
Authors:
María Chávez-Canales; Juan Pablo Arroyo; Benajmin Ko; Norma Vázquez; Rocio Bautista; María Castañeda-Bueno; Norma A Bobadilla; Robert S Hoover; Gerardo Gamba
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of hypertension     Volume:  31     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-10     Completed Date:  2013-07-02     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  303-11     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cells, Cultured
Insulin / pharmacology*
Kidney / drug effects*,  metabolism
Mice
Multiprotein Complexes / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
Sodium Chloride Symporters / metabolism*
TOR Serine-Threonine Kinases / metabolism
Xenopus laevis
Grant Support
ID/Acronym/Agency:
K08 DK070668/DK/NIDDK NIH HHS; K08 DK081728/DK/NIDDK NIH HHS; K08 DK081728/DK/NIDDK NIH HHS; R01 DK-085097/DK/NIDDK NIH HHS; R01 DK064635/DK/NIDDK NIH HHS; R01 DK085097/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Insulin; 0/Multiprotein Complexes; 0/Sodium Chloride Symporters; 0/TOR complex 2; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

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