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Insulin increases the activity of NCC through a PI3K dependent mechanism
Author(s) -
Arroyo Juan Pablo,
Vazquez Norma,
Gamba Gerardo
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1002.12
Subject(s) - insulin , medicine , endocrinology , wortmannin , pi3k/akt/mtor pathway , protein kinase b , insulin receptor , chemistry , biology , phosphorylation , insulin resistance , signal transduction , biochemistry
Obesity and diabetes mellitus are associated with the development of arterial hypertension. One potential mechanism that has been advanced to explain the obesity‐induced hypertension is the effect that insulin may have upon renal salt reabsorption. In this study we assessed the effect of insulin on the activity of the renal NaCl cotransporter, NCC, using the heterologous expression system of Xenopus laevis oocytes. Three days after injection with NCC cRNA the effect of insulin was assessed. NCC activity was measured as the thiazide‐sensitive tracer 22 Na + uptake. We observed that NCC activity is increased by 3‐fold when oocytes were exposed to insulin for 1 to 15 minutes before the uptake. The positive effect was dose and time dependent, with significant effect of insulin as low as with one unit and, as fast as after one minute of exposure. The addition of wortmannin, an inhibitor of phosphatydil‐inositol 3‐kinase (PI3K) completely abrogated the positive effect of insulin on the transporter's activity, without affecting the basal function. The effect of insulin was also abolished by pI103, a PI3K specific inhibitor, and by the specific AKT inhibitor IV. MAP or mTOR kinases inhibitors had no effect. Coinjection of NCC cRNA with WNK4, WNK3, or SPAK cRNA did not affect the activation of NCC by insulin. We conclude that insulin is a powerful activator of NCC and that insulin's effect is translated through the PI3K‐AKT pathway, suggesting that is due to threonine/serine phosphorylation. These observations may have implications to explain the association between obesity and diabetes mellitus with arterial hypertension.