Cross-talk between insulin and IGF-1 receptors in the cortical collecting duct principal cells

Implication for ENaC-mediated NA+ reabsorption

Daria V. Ilatovskaya, Vladislav Levchenko, Michael W Brands, Tengis S. Pavlov, Alexander Staruschenko

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Insulin and IGF-1 are recognized as powerful regulators of the epithelial Na+ channel (ENaC) in the aldosterone-sensitive distal nephron. As previously described, these hormones both acutely increase ENaC activity in freshly isolated split open tubules and cultured principal cortical collecting duct cells. The present study was aimed at differentiating the effects of insulin and IGF-1 on Na+ transport in immortalized mpkCCDcl4 cells and defining their interrelations. We have shown that both insulin and IGF-1 applied basolaterally, but not apically, enhanced transepithelial Na+ transport in the mpkCCDcl4 cell line with EC50 values of 8.8 and 14.5 nM, respectively. Insulin treatment evoked phosphorylation of both insulin and IGF-1 receptors, whereas the effects of IGF-1 were more profound on its own receptor rather than the insulin receptor. AG-1024 and PPP, inhibitors of IGF-1 and insulin receptor tyrosine kinase activity, diminished insulin- and IGF-1-stimulated Na+ transport in mpkCCDcl4 cells. The effects of insulin and IGF-1 on ENaC-mediated currents were found to be additive, with insulin likely stimulating both IGF-1 and insulin receptors. We hypothesize that insulin activates IGF-1 receptors in addition to its own receptors, making the effects of these hormones interconnected

Original languageEnglish (US)
Pages (from-to)F713-F719
JournalAmerican Journal of Physiology - Renal Physiology
Volume308
Issue number7
DOIs
StatePublished - Jan 1 2015

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Epithelial Sodium Channels
IGF Type 1 Receptor
Insulin
Insulin-Like Growth Factor I
Insulin Receptor
Hormones
Nephrons
Aldosterone
Phosphorylation
Cell Line

Keywords

  • Cortical collecting duct
  • Epithelial Na channel
  • Insulin
  • Insulin-like growth factor 1
  • Kidney
  • Natransport
  • Tyrosine kinase

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Cross-talk between insulin and IGF-1 receptors in the cortical collecting duct principal cells : Implication for ENaC-mediated NA+ reabsorption. / Ilatovskaya, Daria V.; Levchenko, Vladislav; Brands, Michael W; Pavlov, Tengis S.; Staruschenko, Alexander.

In: American Journal of Physiology - Renal Physiology, Vol. 308, No. 7, 01.01.2015, p. F713-F719.

Research output: Contribution to journalArticle

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