Title : Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations.

Pub. Date : 2020 Dec

PMID : 33037045






6 Functional Relationships(s)
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Compound Name
Protein Name
Organism
1 The most commonly used oral antidiabetic drug metformin is a substrate of the hepatic uptake transporter OCT1 (SLC22A1). Metformin solute carrier family 22 member 1 Homo sapiens
2 The most commonly used oral antidiabetic drug metformin is a substrate of the hepatic uptake transporter OCT1 (SLC22A1). Metformin solute carrier family 22 member 1 Homo sapiens
3 In conclusion, the contribution of human OCT1 to the cellular uptake of thiamine and especially of metformin may be much lower than that of mouse OCT1. Metformin solute carrier family 22 member 1 Homo sapiens
4 Significance Statement OCT1 is a major hepatic uptake transporter of metformin and thiamine, but we report strong differences in the affinity for both compounds between human and mouse OCT1. Metformin solute carrier family 22 member 1 Homo sapiens
5 Consequently, intrahepatic metformin concentrations could be much higher in mice than in humans, impacting metformin actions and representing a strong limitation of using rodent animal models for predictions of OCT1-related pharmacokinetics and efficacy in humans. Metformin solute carrier family 22 member 1 Homo sapiens
6 Furthermore, OCT1 transmembrane helices TMH2 and TMH3 were identified to confer the observed species-specific differences in metformin affinity. Metformin solute carrier family 22 member 1 Homo sapiens