title: Different effect of testosterone and oestrogen on urinary excretion of metformin via regulating OCTs and MATEs expression in the kidney of mice.
abstract: The aim of this study was to investigate the effect of testosterone and oestrogen on regulating organic cation transporters (Octs) and multidrug and toxin extrusions (Mates) expression in the kidney of mice and urinary excretion of metformin. 8 week-old male db/db mice were treated with estradiol (5 mg/kg), testosterone (50 mg/kg) or olive oil with same volume. Metformin (150 mg/kg) was injected in daily for successive 7 days. Plasma, urine and tissue concentrations of metformin were determined by liquid chromatography-tandem mass spectrometry (LCMS) assay. Western blotting and Real-time PCR analysis were successively used to evaluate the renal protein and mRNA expression of Octs and MATEs. After treatment, the protein expression of Mate1 and Oct2 in testosterone group was significantly increased than those in control group (both P < 0.05). The protein expression of Mate1 and Oct2 in estradiol group was significantly reduced by 29.4% and 43.3%, respectively, compared to those in control group (all P < 0.05). These data showed a good agreement with the change in mRNA level (all P < 0.05). The plasma metformin concentration (ng/ml) in mice treated with estradiol was significantly higher than control and testosterone group (677.56 ± 72.49 versus 293.92 ± 83.27 and 261.46 ± 79.45; P < 0.01). Moreover, testosterone increased the metformin urine excretion of mice while estradiol decreasing (both P < 0.01). Spearman correlation analysis showed that gonadal hormone was closely associated with Mate1 and Oct2 expression and metformin urine excretion in db/db mice (all P < 0.05). Testosterone and oestrogen exerted reverse effect on metformin urinary excretion via regulating Octs and Mates expression in the kidney of mice.
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: He
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Ligen
authors.initials: L
authors.lastname: Ai
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wan
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Taishan
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Junxi
authors.initials: J
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Fengdi
authors.initials: F
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Jiao-Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
mesh_terms: D000818:Animals; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008687:Metformin / Q000493:pharmacokinetics / Q000652:urine*; D008810:Mice, Inbred C57BL; D027701:Organic Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D004967:Estrogens; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; D013739:Testosterone; D008687:Metformin
keywords: MATE1; OCT2; gonadal hormone; kidney; metformin