Document Detail


Insulin activates epithelial sodium channel (ENaC) via phosphoinositide 3-kinase in mammalian taste receptor cells.
MedLine Citation:
PMID:  21106690     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diabetes is a profound disease that results in a severe lack of regulation of systemic salt and water balance. From our earlier work on the endocrine regulation of salt taste at the level of the epithelial sodium channel (ENaC), we have begun to investigate the ability of insulin to alter ENaC function with patch-clamp recording on isolated mouse taste receptor cells (TRCs). In fungiform and vallate TRCs that exhibit functional ENaC currents (e.g., amiloride-sensitive Na(+) influx), insulin (5-20 nM) caused a significant increase in Na(+) influx at -80 mV (EC(50) = 7.53 nM). The insulin-enhanced currents were inhibited by amiloride (30 μM). Similarly, in ratiometric Na(+) imaging using SBFI, insulin treatment (20 nM) enhanced Na(+) movement in TRCs, consistent with its action in electrophysiological assays. The ability of insulin to regulate ENaC function is dependent on the enzyme phosphoinositide 3-kinase since treatment with the inhibitor LY294002 (10 μM) abolished insulin-induced changes in ENaC. To test the role of insulin in the regulation of salt taste, we have characterized behavioral responses to NaCl using a mouse model of acute hyperinsulinemia. Insulin-treated mice show significant avoidance of NaCl at lower concentrations than the control group. Interestingly, these differences between groups were abolished when amiloride (100 μM) was added into NaCl solutions, suggesting that insulin was regulating ENaC. Our results are consistent with a role for insulin in maintaining functional expression of ENaC in mouse TRCs.
Authors:
Arian F Baquero; Timothy A Gilbertson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-24
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  300     ISSN:  1522-1563     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-29     Completed Date:  2011-05-20     Revised Date:  2012-04-02    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C860-71     Citation Subset:  IM    
Affiliation:
Department of Biology and The Center for Advanced Nutrition, Utah State University, Logan, USA. arian.baquero@ucdenver.edu
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MeSH Terms
Descriptor/Qualifier:
Amiloride / metabolism
Animals
Behavior, Animal / drug effects
Epithelial Sodium Channel / genetics,  metabolism*
Insulin / pharmacology*
Insulin Receptor Substrate Proteins / genetics,  metabolism
Male
Mice
Mice, Inbred C57BL
Patch-Clamp Techniques
Phosphatidylinositol 3-Kinases / genetics,  metabolism*
Phosphatidylinositols / chemistry,  metabolism
Receptor, Insulin / metabolism
Receptors, G-Protein-Coupled / genetics,  metabolism*
Sodium / metabolism
Sodium Channel Blockers / metabolism
Sodium, Dietary
Taste Buds / cytology*,  drug effects*,  metabolism
Grant Support
ID/Acronym/Agency:
DC02507/DC/NIDCD NIH HHS; P30 DC04657/DC/NIDCD NIH HHS; R01 DC006021/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/Epithelial Sodium Channel; 0/Insulin; 0/Insulin Receptor Substrate Proteins; 0/Irs2 protein, mouse; 0/Phosphatidylinositols; 0/Receptors, G-Protein-Coupled; 0/Sodium Channel Blockers; 0/Sodium, Dietary; 2609-46-3/Amiloride; 7440-23-5/Sodium; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Receptor, Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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