Insulin activates Na(+)/H(+) exchanger 3: biphasic response and glucocorticoid dependence.
Publisher DOI
PubMed ID
12167605
Abstract
Insulin is an important regulator of renal salt and water excretion, and hyperinsulinemia has been implicated to play a role in hypertension. One of the target proteins of insulin action in the kidney is Na(+)/H(+) exchanger 3 (NHE3), a principal Na(+) transporter responsible for salt absorption in the mammalian proximal tubule. The molecular mechanisms involved in activation of NHE3 by insulin have not been studied so far. In opossum kidney (OK) cells, insulin increased Na(+)/H(+) exchange activity in a time- and concentration-dependent manner. This effect is due to activation of NHE3 as it persisted after pharmacological inhibition of NHE1 and NHE2. In the early phase of stimulation (2-12 h), NHE3 activity was increased without changes in NHE3 protein and mRNA. At 24 h, enhanced NHE3 activity was accompanied by an increase in total and cell surface NHE3 protein and NHE3 mRNA abundance. All the effects of insulin on NHE3 activity, protein, and mRNA were amplified in the presence of hydrocortisone. These results suggest that insulin stimulates renal tubular NHE3 activity via a biphasic mechanism involving posttranslational factors and an increase in NHE3 gene expression and the effects are dependent on the permissive action of hydrocortisone.
Date Issued
2002-09
Publication Type
Article
Subject(s)
Language(s)
en
Author(s)
Klisic, Jelena | |
Hu, Ming Chang | |
Nief, Vera | |
Reyes, Livia | |
Moe, Orson W | |
Ambühl, Patrice M |
Additional Credits
Journal
American journal of physiology - renal physiology
Publisher
American Physiological Society
ISSN
0363-6127
Access(Rights)
restricted