Insulin-like growth factor-1 (IGF-1) inhibits the basolateral Cl channels in the thick ascending limb of the rat kidney.

Biochimica Et Biophysica Acta
Lijun WangRuimin Gu

Abstract

The aim of the present study is to test the hypothesis that insulin-like-growth factor-1 (IGF-1) plays a role in the regulation of basolateral Cl channels in the thick ascending limb (TAL). The patch-clamp experiments demonstrated that application of IGF-I or insulin inhibited the basolateral 10-pS Cl channels. However, the concentration of insulin required for the inhibition of the Cl channels by 50% (K(1/2)) was ten times higher than those of IGF-1. The inhibitory effect of IGF-I on the 10-pS Cl channels was blocked by suppressing protein tyrosine kinase or by blocking phosphoinositide 3-kinase (PI3K). In contrast, inhibition of phospholipase C (PLC) failed to abolish the inhibitory effect of IGF-1 on the Cl channels in the TAL. Western blot analysis demonstrated that IGF-1 significantly increased the phosphorylation of phospholipid-dependent kinase (PDK) at serine residue 241 (Ser(241)) and AKT at Ser(473) in the isolated medullary TAL. Moreover, inhibition of PI3K with LY294002 abolished the effect of IGF-1 on the phosphorylation of PDK and AKT. The notion that the effect of IGF-1 on the 10-pS Cl channels was induced by stimulation of PDK-AKT-mTOR pathway was further suggested by the finding that rapamycin completely abolis...Continue Reading

Citations

Mar 8, 2017·Journal of the American Heart Association·Jian YangChunyu Zeng
Oct 24, 2014·American Journal of Physiology. Renal Physiology·Oleg ZaikaOleh Pochynyuk
Mar 26, 2016·Frontiers in Neuroscience·Simona GradariJosé L Trejo
Jan 23, 2016·American Journal of Physiology. Renal Physiology·Oleg ZaikaOleh Pochynyuk

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