Thiazolidinediones enhance sodium-coupled bicarbonate absorption from renal proximal tubules via PPARγ-dependent nongenomic signaling

Yoko Endo, Masashi Suzuki, Hideomi Yamada, Shoko Horita, Motoei Kunimi, Osamu Yamazaki, Ayumi Shirai, Motonobu Nakamura, Naoyuki Iso-O, Yuehong Li, Masumi Hara, Kazuhisa Tsukamoto, Nobuo Moriyama, Akihiko Kudo, Hayato Kawakami, Toshimasa Yamauchi, Naoto Kubota, Takashi Kadowaki, Haruki Kume, Yutaka EnomotoYukio Homma, George Seki, Toshiro Fujita

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Thiazolidinediones (TZDs) improve insulin resistance by activating a nuclear hormone receptor, peroxisome proliferator-activated receptor γ (PPARγ). However, the use of TZDs is associated with plasma volume expansion through a mechanism that remains to be clarified. Here we showed that TZDs rapidly stimulate sodium-coupled bicarbonate absorption from the renal proximal tubule in vitro and in vivo. TZD-induced transport stimulation is dependent on PPARγ-Src-EGFR-ERK and observed in rat, rabbit and human, but not in mouse proximal tubules where Src-EGFR is constitutively activated. The existence of PPARγ-Src-dependent nongenomic signaling, which requires the ligand-binding ability, but not the transcriptional activity of PPARγ, is confirmed in mouse embryonic fibroblast cells. The enhancement of the association between PPARγ and Src by TZDs supports an indispensable role of Src in this signaling. These results suggest that the PPARγ-dependent nongenomic stimulation of renal proximal transport is also involved in TZD-induced volume expansion.

Original languageEnglish
Pages (from-to)550-561
Number of pages12
JournalCell Metabolism
Volume13
Issue number5
DOIs
Publication statusPublished - 2011 May 4

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Thiazolidinediones enhance sodium-coupled bicarbonate absorption from renal proximal tubules via PPARγ-dependent nongenomic signaling'. Together they form a unique fingerprint.

  • Cite this

    Endo, Y., Suzuki, M., Yamada, H., Horita, S., Kunimi, M., Yamazaki, O., Shirai, A., Nakamura, M., Iso-O, N., Li, Y., Hara, M., Tsukamoto, K., Moriyama, N., Kudo, A., Kawakami, H., Yamauchi, T., Kubota, N., Kadowaki, T., Kume, H., ... Fujita, T. (2011). Thiazolidinediones enhance sodium-coupled bicarbonate absorption from renal proximal tubules via PPARγ-dependent nongenomic signaling. Cell Metabolism, 13(5), 550-561. https://doi.org/10.1016/j.cmet.2011.02.015