Tyrosine kinase, phosphatidylinositol 3-kinase, and protein kinase C regulate insulin-stimulated NaCl absorption in the thick ascending limb

Osamu Ito, Yoshiaki Kondo, Minako Oba, Nobuyuki Takahashi, Ken Omata, Keishi Abe

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We have previously shown a direct stimulatory effect of insulin on NaCl absorption in the medullary thick ascending limb of Henle's loop (mTAP). To further investigate the signal transduction involved, we determined whether tyrosine kinase, phosphatidylinositol 3-kinase (PI3-kinase), and/or protein kinase C (PKC) regulate insulin-stimulated NaCl absorption in the mTAL by in vitro microperfusion methods. In control experiments, insulin increased transepithelial voltage (V(te)) and net lumen-to-bath Cl- flux (J(Cl)). Genistein and methyl 2,5-dihydroxycinnamate, two specific tyrosine kinase inhibitors, abolished the effects of insulin. Wortmannin, a specific PI3-kinase inhibitor, inhibited the action of insulin. The effects of insulin also were inhibited by staurosporin and calphostin C, which are dissimilar inhibitors of PKC. These results indicate that insulin stimulates NaCl absorption in the mTAL through tyrosine kinase, PI3-kinase, and PKC-mediated mechanisms. Moreover, because we have reported previously that insulin causes no detectable change in cytosolic free Ca2+ in the mTAL cells, the present results also suggest that insulin-induced PKC activation is not related to inositol 1,4,5-triphosphate (IP3) production.

Original languageEnglish
Pages (from-to)1037-1041
Number of pages5
JournalKidney international
Volume51
Issue number4
DOIs
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Nephrology

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