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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin.

Metformin, a biguanide, is widely used as an oral hypoglycemic agent for the treatment of type 2 diabetes mellitus. The purpose of the present study was to investigate the role of organic cation transporter 1 (Oct1) in the disposition of metformin. Transfection of rat Oct1 cDNA results in the time-dependent and saturable uptake of metformin by the Chinese hamster ovary cell line with K(m) and V(max) values of 377 microM and 1386 pmol/min/mg of protein, respectively. Buformin and phenformin, two other biguanides, were also transported by rOct1 with a higher affinity than metformin: their K(m) values were 49 and 16 microM, respectively. To investigate the role of Oct1 in the disposition of metformin, the tissue distribution of metformin was determined in Oct1 gene-knockout mice after i.v. administration. Distribution of metformin to the liver in Oct1(-/-) mice was more than 30 times lower than that in Oct1(+/+) mice, and can be accounted for by the extracellular space. Distribution to the small intestine was also decreased in Oct1(-/-) mice, whereas that to the kidney as well as the urinary excretion profile showed only minimal differences. In conclusion, the present findings suggest that Oct1 is responsible for the hepatic uptake as well as playing a role in the intestinal uptake of metformin, whereas the renal distribution and excretion are mainly governed by other transport mechanism(s).[1]

References

  1. Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin. Wang, D.S., Jonker, J.W., Kato, Y., Kusuhara, H., Schinkel, A.H., Sugiyama, Y. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
 
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