| First Author | Endo Y | Year | 2011 |
| Journal | Cell Metab | Volume | 13 |
| Issue | 5 | Pages | 550-61 |
| PubMed ID | 21531337 | Mgi Jnum | J:175814 |
| Mgi Id | MGI:5287348 | Doi | 10.1016/j.cmet.2011.02.015 |
| Citation | Endo Y, et al. (2011) Thiazolidinediones enhance sodium-coupled bicarbonate absorption from renal proximal tubules via PPARgamma-dependent nongenomic signaling. Cell Metab 13(5):550-61 |
| abstractText | Thiazolidinediones (TZDs) improve insulin resistance by activating a nuclear hormone receptor, peroxisome proliferator-activated receptor gamma (PPARgamma). 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 PPARgamma-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 PPARgamma-Src-dependent nongenomic signaling, which requires the ligand-binding ability, but not the transcriptional activity of PPARgamma, is confirmed in mouse embryonic fibroblast cells. The enhancement of the association between PPARgamma and Src by TZDs supports an indispensable role of Src in this signaling. These results suggest that the PPARgamma-dependent nongenomic stimulation of renal proximal transport is also involved in TZD-induced volume expansion. |
