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Author: Admin | 2025-04-28
Our body through organic cation transporters (OCT). At intestinal pH, metformin exists as a cationic hydrophilic base and possesses physiochemical properties that hinder its passive diffusion across cell membranes [13]. While metformin absorption is believed to be primarily through plasma membrane monoamine transporters (PMAT) of enterocytes, studies have suggested a role for OCT1 and OCT3 in this process. The post-absorption plasma concentration levels of metformin range from 54 to 4133 ng/mL, but individuals with OCT1 variants have lower plasma concentrations [14].Metformin enters hepatocytes through OCT1 and OCT3 transporters [15,16]. It is generally accepted that metformin antagonizes the 5′-AMP-activated protein kinase (AMPK) to impact cellular energy stress. It inhibits complex I of the mitochondrial electron transport chain, decreases adenosine triphosphate (ATP) production, and increases the AMP/ATP ratio, which is detected by the AMPK. Metformin-induced AMPK activation diminishes acetyl-CoA carboxylase (ACC) activity, promotes fatty acid oxidation, and hinders lipogenic enzyme expression [17]. Through AMPK activation, metformin also inhibits the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling [18]. Conversely, studies also suggest that metformin exerts its effects through an AMPK-independent mechanism, inhibiting phosphatidylinositol 3-kinase/Akt/mTOR (PI3K/AKT/mTOR) pathways [19].About 90% of absorbed metformin is eliminated within the first 24 h following oral administration, with a plasma clearance half-life of approximately 6.2 h. Meanwhile, the removal half-life of metformin in the blood is roughly 17.6 h [20]. Although metformin is not metabolized, several organs are involved in its elimination from the human body. Excretion of metformin from the liver is facilitated by organic cation
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