title: Cross-talk between insulin and IGF-1 receptors in the cortical collecting duct principal cells: implication for ENaC-mediated Na+ reabsorption.
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.
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
authors: Daria V
authors: DV
authors: Ilatovskaya
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
authors: Vladislav
authors: V
authors: Levchenko
authors: Department of Physiology, Georgia Regents University, Augusta, Georgia.
authors: Michael W
authors: MW
authors: Brands
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
authors: Tengis S
authors: TS
authors: Pavlov
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; and staruschenko@mcw.edu.
authors: Alexander
authors: A
authors: Staruschenko
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D051379:Mice; D009399:Nephrons / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000378:metabolism*
chemical_list: D053503:Epithelial Sodium Channels; D007328:Insulin; D007334:Insulin-Like Growth Factor I; D012964:Sodium; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin
keywords: Na+ transport; cortical collecting duct; epithelial Na+ channel; insulin; insulin-like growth factor 1; kidney; tyrosine kinase
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