The Impact of Solute Carrier (SLC) Drug Uptake Transporter Loss in Human and Rat Cryopreserved Hepatocytes on Clearance Predictions.

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Biochimica et Biophysica Acta (BBA) - General Subjects 2014, 1840 The anti-proliferative effect of metformin in triple-negative MDA-MB-231 breast cancer cells is highly dependent on glucose concentration: Implications for cancer therapy and prevention. Physiological and Pathophysiological Regulation of Transporters for Organic Cations. Rapid Method To Determine Intracellular Drug Concentrations in Cellular Uptake Assays: Application to Metformin in Organic Cation Transporter 1-Transfected Human Embryonic Kidney 293 Cells. Structure and function of multidrug and toxin extrusion proteins (MATEs) and their relevance to drug therapy and personalized medicine. Nies, Katja Damme, Stephan Kruck, Elke Schaeffeler, Matthias Schwab.

Diabetes, Obesity and Metabolism 2017, 19 Metformin-associated lactic acidosis (MALA): Moving towards a new paradigm. Jean-Daniel Lalau, Farshad Kajbaf, Alessandro Protti, Mette M.Ischemia/reperfusion-associated tubular cells injury in renal transplantation: Can metabolomics inform about mechanisms and help identify new therapeutic targets?. Chantal Barin-Le Guellec, Bérenger Largeau, Delphine Bon, Pierre Marquet, Thierry Hauet.Modulation of YrdC promotes hepatocellular carcinoma progression via MEK/ERK signaling pathway. Shiqiong Huang, Peng Zhu, Bao Sun, Jun Guo, Honghao Zhou, Yan Shu, Qing Li.Organic Cation Transporters in Health and Disease. Effects of Ischemia-Reperfusion on Tubular Cell Membrane Transporters and Consequences in Kidney Transplantation. Quentin Faucher, Hugo Alarcan, Pierre Marquet, Chantal Barin-Le Guellec.Organic Cation Transporter (OCT/OCTN) Expression at Brain Barrier Sites: Focus on CNS Drug Delivery. Divergent Regulation of OCT and MATE Drug Transporters by Cadmium Exposure. Hong Yang, Shiwei Zhou, Dong Guo, Obinna N.Incorporation of a Biguanide Scaffold Enhances Drug Uptake by Organic Cation Transporters 1 and 2.

Coutinho, Wei Yang, Hong Yang, Fengtian Xue, and Yan Shu. This article is cited by 13 publications. The regulation by IRIP on transporter activities likely occurs at a post-transcriptional level, and future studies are needed to characterize the exact mechanism.

Importantly, we provide in vivo evidence for such modulation that may cause an alteration in drug disposition. In conclusion, IRIP negatively modulates the function of OCT1 and MATE1 in cells. In addition, we observed that the expression of IRIP was approximately half ( P < 0.01) in ob/ob mice when compared to their lean littermates, with significant increases in hepatic Oct1 protein expression and metformin accumulation. By overexpressing IRIP in mouse liver via hydrodynamic tail vein injection, we demonstrated that increased IRIP expression could cause a significant reduction in hepatic accumulation of metformin ( P < 0.01). IRIP overexpression decreased the membrane localization of transporter proteins without any changes in transcript levels in cells. In contrast, knockdown of IRIP by small hairpin RNA (shRNA) increased the transporter activities in vitro. In the uptake studies in the human embryonic kidney 293 cells overexpressing IRIP with and without OCT1 or MATE1, IRIP overexpression was found to significantly inhibit the uptake of 1-methyl-4-phenylpyridinium mediated by OCT1 or MATE1. The goal of this study is to determine whether IRIP regulates the activities of OCT1 and MATE1, and hence the disposition in vivo of their substrate metformin, a therapeutic drug for diabetes and other obesity-related syndromes. The recently identified ischemia/reperfusion-inducible protein (IRIP) has been reported to negatively modulate the activities of several transporters in cell culture systems.

Irip activation code