uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Trafficking of ENaC subunits in response to acute insulin in mouse kidney
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrativ Fysiologi. (Nordquist)
2007 (English)In: American Journal of Physiology - Renal Physiology, ISSN 0363-6127, E-ISSN 1522-1466, Vol. 293, no 1, F178-F185 p.Article in journal (Refereed) Published
Abstract [en]

Studies done in cell culture have demonstrated that insulin activates the epithelial sodium channel (ENaC) via a variety of mechanisms. However, to date, upregulation of ENaC in native renal tissue by in vivo administration of insulin has not been demonstrated. To address this, we injected 6-mo-old male C57BL/CBA mice (n = 14/group) intraperitoneally with vehicle or 0.5 U/kg body wt insulin and examined short-term (1-2 h) sodium excretion and kidney ENaC subunits (alpha, beta, and gamma) and serum and glucocorticoid-induced kinase (SGK-1) regulation. Insulin resulted in a significant reduction in urine sodium (by approximately 80%) that was restored by intraperitoneal administration of the ENaC antagonist, benzamil (1.4 mg/kg body wt). Differential centrifugation followed by Western blotting of whole kidney revealed significantly increased band densities (by 26-103%) for insulin- relative to vehicle-treated mice for alpha- and gamma-ENaC in the homogenate (H), and plasma membrane-enriched fraction (MF), with no difference in the vesicle-enriched fraction (VF). Similarly, beta-ENaC was significantly increased in MF (by 45%) but no change in the H. It was, however, significantly decreased in the VF (by 28%) with insulin. In agreement, immunoperoxidase labeling demonstrated relatively stronger apical, relative to cytosolic, localization of alpha-, beta-, and gamma-ENaC with insulin, whereas, with vehicle, labeling was fairly evenly dispersed throughout collecting duct principal cells. Furthermore, Western blotting showed insulin increased SGK-1 (by 75%) and phosphorylated-SGK band densities (by 30%) but only in the MF. These studies demonstrate novel in vivo regulation of renal ENaC activity and subunit proteins and SGK-1 by insulin in the acute time frame in the mouse.

Place, publisher, year, edition, pages
2007. Vol. 293, no 1, F178-F185 p.
Keyword [en]
epithelial sodium channel, SGK-1, hyperinsulinemia
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-104059DOI: 10.1152/ajprenal.00447.2006ISI: 000247850500025PubMedID: 17389677OAI: oai:DiVA.org:uu-104059DiVA: diva2:220125
Available from: 2009-05-29 Created: 2009-05-27 Last updated: 2011-11-17Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Nordquist, Lina
By organisation
Integrativ Fysiologi
In the same journal
American Journal of Physiology - Renal Physiology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 172 hits
ReferencesLink to record
Permanent link

Direct link