Polymorphism in human organic cation transporters and metformin action

Hiroshi Takane, Eriko Shikata, Kenji Otsubo, Shun Higuchi, Ichiro Ieiri

Research output: Contribution to journalReview article

94 Citations (Scopus)

Abstract

Considerable interindividual variabilities in clinical efficacy and adverse events are sometimes recognized in the treatment of Type 2 diabetes mellitus with oral antihyperglycemic drugs. Metformin is the most commonly used biguanide in clinical practice, and also improves insulin resistance and reduces cardiovascular risk. However, certain patients taking metformin do not respond sufficiently. The molecular reasons for the variability in response to metformin are not clear. However, it has been recently suggested that genetic factors may be responsible for the variability. Metformin is not metabolized but is transported by at least two organic cation transporters (OCT), OCT1 and OCT2. Recently, genetic polymorphisms in OCT1 and OCT2 have been found to be associated with changes in pharmacokinetic/pharmacodynamic responses to substrate drugs. This review focuses on the impact of the genetic polymorphism of organic cation transporters on transport activity, and the implications for the clinical efficacy of metformin.

Original languageEnglish
Pages (from-to)415-422
Number of pages8
JournalPharmacogenomics
Volume9
Issue number4
DOIs
Publication statusPublished - Apr 1 2008

Fingerprint

Metformin
Cations
Genetic Polymorphisms
Biguanides
Hypoglycemic Agents
Pharmaceutical Preparations
Type 2 Diabetes Mellitus
Insulin Resistance
Pharmacokinetics

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

Cite this

Polymorphism in human organic cation transporters and metformin action. / Takane, Hiroshi; Shikata, Eriko; Otsubo, Kenji; Higuchi, Shun; Ieiri, Ichiro.

In: Pharmacogenomics, Vol. 9, No. 4, 01.04.2008, p. 415-422.

Research output: Contribution to journalReview article

Takane, Hiroshi ; Shikata, Eriko ; Otsubo, Kenji ; Higuchi, Shun ; Ieiri, Ichiro. / Polymorphism in human organic cation transporters and metformin action. In: Pharmacogenomics. 2008 ; Vol. 9, No. 4. pp. 415-422.
@article{84b7618d372e47738e2ff1e167e390d4,
title = "Polymorphism in human organic cation transporters and metformin action",
abstract = "Considerable interindividual variabilities in clinical efficacy and adverse events are sometimes recognized in the treatment of Type 2 diabetes mellitus with oral antihyperglycemic drugs. Metformin is the most commonly used biguanide in clinical practice, and also improves insulin resistance and reduces cardiovascular risk. However, certain patients taking metformin do not respond sufficiently. The molecular reasons for the variability in response to metformin are not clear. However, it has been recently suggested that genetic factors may be responsible for the variability. Metformin is not metabolized but is transported by at least two organic cation transporters (OCT), OCT1 and OCT2. Recently, genetic polymorphisms in OCT1 and OCT2 have been found to be associated with changes in pharmacokinetic/pharmacodynamic responses to substrate drugs. This review focuses on the impact of the genetic polymorphism of organic cation transporters on transport activity, and the implications for the clinical efficacy of metformin.",
author = "Hiroshi Takane and Eriko Shikata and Kenji Otsubo and Shun Higuchi and Ichiro Ieiri",
year = "2008",
month = "4",
day = "1",
doi = "10.2217/14622416.9.4.415",
language = "English",
volume = "9",
pages = "415--422",
journal = "Pharmacogenomics",
issn = "1462-2416",
publisher = "Future Medicine Ltd.",
number = "4",

}

TY - JOUR

T1 - Polymorphism in human organic cation transporters and metformin action

AU - Takane, Hiroshi

AU - Shikata, Eriko

AU - Otsubo, Kenji

AU - Higuchi, Shun

AU - Ieiri, Ichiro

PY - 2008/4/1

Y1 - 2008/4/1

N2 - Considerable interindividual variabilities in clinical efficacy and adverse events are sometimes recognized in the treatment of Type 2 diabetes mellitus with oral antihyperglycemic drugs. Metformin is the most commonly used biguanide in clinical practice, and also improves insulin resistance and reduces cardiovascular risk. However, certain patients taking metformin do not respond sufficiently. The molecular reasons for the variability in response to metformin are not clear. However, it has been recently suggested that genetic factors may be responsible for the variability. Metformin is not metabolized but is transported by at least two organic cation transporters (OCT), OCT1 and OCT2. Recently, genetic polymorphisms in OCT1 and OCT2 have been found to be associated with changes in pharmacokinetic/pharmacodynamic responses to substrate drugs. This review focuses on the impact of the genetic polymorphism of organic cation transporters on transport activity, and the implications for the clinical efficacy of metformin.

AB - Considerable interindividual variabilities in clinical efficacy and adverse events are sometimes recognized in the treatment of Type 2 diabetes mellitus with oral antihyperglycemic drugs. Metformin is the most commonly used biguanide in clinical practice, and also improves insulin resistance and reduces cardiovascular risk. However, certain patients taking metformin do not respond sufficiently. The molecular reasons for the variability in response to metformin are not clear. However, it has been recently suggested that genetic factors may be responsible for the variability. Metformin is not metabolized but is transported by at least two organic cation transporters (OCT), OCT1 and OCT2. Recently, genetic polymorphisms in OCT1 and OCT2 have been found to be associated with changes in pharmacokinetic/pharmacodynamic responses to substrate drugs. This review focuses on the impact of the genetic polymorphism of organic cation transporters on transport activity, and the implications for the clinical efficacy of metformin.

UR - http://www.scopus.com/inward/record.url?scp=44949087480&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44949087480&partnerID=8YFLogxK

U2 - 10.2217/14622416.9.4.415

DO - 10.2217/14622416.9.4.415

M3 - Review article

C2 - 18384255

AN - SCOPUS:44949087480

VL - 9

SP - 415

EP - 422

JO - Pharmacogenomics

JF - Pharmacogenomics

SN - 1462-2416

IS - 4

ER -