Molecules, Vol. 25, Pages 392: PPAR α-Dependent Modulation by Metformin of the Expression of OCT-2 and MATE-1 in the Kidney of Mice

Molecules, Vol. 25, Pages 392: PPARα-Dependent Modulation by Metformin of the Expression of OCT-2 and MATE-1 in the Kidney of Mice Molecules doi: 10.3390/molecules25020392 Authors: Adriano Cleis Arruda Mauro Sérgio Perilhão Warley Almeida Santos Marcos Fernandes Gregnani Alexandre Budu José Cesar Rosa Neto Gabriel Rufino Estrela Ronaldo Carvalho Araujo Metformin is the first-line drug for type 2 diabetes mellitus control. It is established that this drug traffics through OCT-2 and MATE-1 transporters in kidney tubular cells and is excreted in its unaltered form in the urine. Hereby, we provide evidence that points towards the metformin-dependent upregulation of OCT-2 and MATE-1 in the kidney via the transcription factor proliferator-activated receptor alpha (PPARα). Treatment of wild type mice with metformin led to the upregulation of the expression of OCT-2 and MATE-1 by 34% and 157%, respectively. An analysis in a kidney tubular cell line revealed that metformin upregulated PPARα and OCT-2 expression by 37% and 299% respectively. MK-886, a PPARα antagonist, abrogated the OCT-2 upregulation by metformin and reduced MATE-1 expression. Conversely, gemfibrozil, an agonist of PPARα, elicited the increase of PPARα, OCT-2, and MATE-1 expression by 115%, 144%, and 376%, respectively. PPARα knockout mice failed to upregulate both the expression of OCT-2 and MATE-1 in the kid...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research