Human organic cation transporter 1 / OCT1 / SLC22A1

evidence_access

Primary abstract

experimental_model

Human transporter expressed in HEK293 cells; radiolabeled agmatine.

limitations

An in vitro Km is not a target blood concentration or oral bioavailability estimate.

nutrient_topic

Agmatine Sulfate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Agmatine Sulfate

plain_language

A transporter can admit the molecule, but its affinity matters.

primary_references

OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

transport_effect

raises Expression increased concentration-dependent agmatine transport into HEK293 cells.

transport_pool

the expressing cell Expression increased concentration-dependent agmatine transport into HEK293 cells.

Agmatine Sulfate: transport, guanidino metabolism, ion channels and cross-nutrient mechanisms (2026-09-20) · lines 20–26

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transporter expressed in HEK293 cells; radiolabeled agmatine. · source_derived_draft · unverified_draft

## agmatine-sulfate-oct1 A transporter can admit the molecule, but its affinity matters. Human OCT1 expression increased concentration-dependent agmatine transport in HEK293 cells, with Km 18.73 ± 4.86 mM. Model: Human transporter expressed in HEK293 cells; radiolabeled agmatine. Limitations: An in vitro Km is not a target blood concentration or oral bioavailability estimate. Evidence access: Primary abstract OCT2 and MATE1 provide bidirectional agmatine transport. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21128598/ · DOI 10.1021/mp100180a

evidence_span

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experimental_model

Human versus mouse transporter kinetics in transfected HEK293 cells

exposure

Thiamine and metformin transport; transporter chimeras

limitations

Human OCT1 affinity for thiamine was substantially lower than mouse Oct1. This is a shared-transporter connection, not proof berberine causes B1 deficiency.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human OCT1 and mouse Oct1

plain_language

Vitamin B1 shares this transporter, but the mouse and human versions behave differently.

primary_references

[berberine-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

tissue_or_cell_type

Cellular thiamine uptake

transport_effect

raises A species-affinity comparison, but the measurement is thiamine carried into the expressing cell, which stands for the hepatocyte.

transport_pool

the hepatocyte interior A species-affinity comparison, but the measurement is thiamine carried into the expressing cell, which stands for the hepatocyte.

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 298–309

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human versus mouse transporter kinetics in transfected HEK293 cells · source_derived_draft · unverified_draft

### berberine-human-thiamine-transport Human OCT1 transported thiamine with approximately 9.5-fold lower affinity than mouse Oct1. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B1 shares this transporter, but the mouse and human versions behave differently. organism: Human OCT1 and mouse Oct1 tissue_or_cell_type: Cellular thiamine uptake experimental_model: Human versus mouse transporter kinetics in transfected HEK293 cells limitations: Human OCT1 affinity for thiamine was substantially lower than mouse Oct1. This is a shared-transporter connection, not proof berberine causes B1 deficiency. exposure: Thiamine and metformin transport; transporter chimeras evidence_span: {"source_cache": "artifacts/berberine-research/33037045.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "61d53435dfc952ba419da91767e79c07d75e2a432d9d4a2afd0d8d2560d570fd", "start_char": 0, "end_char": 2298, "text_sha256": "61d53435dfc952ba419da91767e79c07d75e2a432d9d4a2afd0d8d2560d570fd"} [berberine-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

evidence_span

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experimental_model

Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics

exposure

Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis

limitations

Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human participants and human OCT1; Oct1/2-deficient mice in separate arms

plain_language

A cell-transport difference did not translate into a detected blood-level difference.

primary_references

[berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454

tissue_or_cell_type

Liver transport and systemic exposure

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 259–270

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics · source_derived_draft · unverified_draft

### berberine-oct1-genotype-null Poor OCT1 transporters did not show a difference in human berberine pharmacokinetics despite reduced uptake by variant OCT1 in vitro. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cell-transport difference did not translate into a detected blood-level difference. organism: Human participants and human OCT1; Oct1/2-deficient mice in separate arms tissue_or_cell_type: Liver transport and systemic exposure experimental_model: Transporter kinetics, mouse perfusion and human genotype-stratified pharmacokinetics limitations: Human OCT1 null finding differs from cellular and mouse findings. Sex-specific CYP2D6 result is not a universal rule for all formulations or a dosing algorithm. exposure: Oral berberine; OCT1 and CYP2D6 functional variants; sex-stratified analysis evidence_span: {"source_cache": "artifacts/berberine-research/39488825.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33", "start_char": 0, "end_char": 1787, "text_sha256": "ba324da62a36391435595fd7c4de2a848aae714abd4df063433362e4fdddce33"} [berberine-p39488825] Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans. (2025). https://pubmed.ncbi.nlm.nih.gov/39488825/ DOI: 10.1002/cpt.3454

evidence_span

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experimental_model

Polarized transporter-transfected MDCKII cells

exposure

Berberine transport kinetics and transporter inhibition

limitations

Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human OCT1, OCT2 and ABCB1 in engineered canine cells

plain_language

Berberine uses a separately identified organic-cation uptake transporter.

primary_references

[berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x

tissue_or_cell_type

Basolateral uptake and apical export

transport_effect

raises Berberine uptake measured in transfected cells, which stand for the hepatocyte, with a reported Km of 14.8 micromolar.

transport_pool

the hepatocyte interior Berberine uptake measured in transfected cells, which stand for the hepatocyte, with a reported Km of 14.8 micromolar.

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 207–218

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized transporter-transfected MDCKII cells · source_derived_draft · unverified_draft

### berberine-uptake-oct1 Human OCT1 transported berberine in transfected cells, with reported Km 14.8 micromolar. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Berberine uses a separately identified organic-cation uptake transporter. organism: Human OCT1, OCT2 and ABCB1 in engineered canine cells tissue_or_cell_type: Basolateral uptake and apical export experimental_model: Polarized transporter-transfected MDCKII cells limitations: Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck. exposure: Berberine transport kinetics and transporter inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"} [berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x

evidence_span

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experimental_model

Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling

exposure

Metformin and thiamine uptake kinetics; transmembrane-helix substitutions

limitations

A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human and mouse orthologues side by side

plain_language

The mouse liver concentrates this drug far more than the human liver does.

primary_references

[metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

tissue_or_cell_type

Hepatic uptake

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 320–331

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling · source_derived_draft · unverified_draft

### metformin-oct1-species-metformin The affinity for metformin was 4.9-fold lower in human than in mouse OCT1, giving a 6.5-fold lower intrinsic clearance and an estimated liver-to-blood partition coefficient of 3.34 in human compared with 14.4 in mouse. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The mouse liver concentrates this drug far more than the human liver does. organism: Human and mouse orthologues side by side tissue_or_cell_type: Hepatic uptake experimental_model: Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling limitations: A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement. exposure: Metformin and thiamine uptake kinetics; transmembrane-helix substitutions evidence_span: {"source_cache": "artifacts/metformin-research/33037045.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67", "start_char": 0, "end_char": 2296, "text_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67"} [metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

evidence_span

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experimental_model

Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling

exposure

Metformin and thiamine uptake kinetics; transmembrane-helix substitutions

limitations

A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human and mouse orthologues side by side

plain_language

The same species gap applies to the vitamin the transporter carries.

primary_references

[metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

tissue_or_cell_type

Hepatic uptake

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 333–344

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling · source_derived_draft · unverified_draft

### metformin-oct1-species-thiamine The affinity for thiamine was 9.5-fold lower in human than in mouse OCT1. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The same species gap applies to the vitamin the transporter carries. organism: Human and mouse orthologues side by side tissue_or_cell_type: Hepatic uptake experimental_model: Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling limitations: A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement. exposure: Metformin and thiamine uptake kinetics; transmembrane-helix substitutions evidence_span: {"source_cache": "artifacts/metformin-research/33037045.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67", "start_char": 0, "end_char": 2296, "text_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67"} [metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

evidence_span

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experimental_model

Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake

exposure

Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice

limitations

Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Mouse and human transporter

plain_language

The transporter that carries the drug into the liver normally carries vitamin B1.

primary_references

[metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

tissue_or_cell_type

Liver and intestine

transport_effect

raises Identified by isotopic uptake as a principal endogenous substrate.

transport_pool

the expressing cell Identified by isotopic uptake as a principal endogenous substrate.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1230–1241

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake · source_derived_draft · unverified_draft

### metformin-oct1-thiamine-substrate Metabolomic and isotopic uptake methods identified thiamine as a principal endogenous substrate of OCT1. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The transporter that carries the drug into the liver normally carries vitamin B1. organism: Mouse and human transporter tissue_or_cell_type: Liver and intestine experimental_model: Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake limitations: Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype. exposure: Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice evidence_span: {"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"} [metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

evidence_span

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experimental_model

Polarized transporter-transfected MDCKII cells

exposure

Berberine transport kinetics and transporter inhibition

limitations

Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck.

nutrient_topic

Berberine research collection; topical membership is not evidence of a direct dietary effect. · Berberine

organism

Human OCT1, OCT2 and ABCB1 in engineered canine cells

plain_language

An entry transporter and an exit pump can work in sequence.

primary_references

[berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x

tissue_or_cell_type

Basolateral uptake and apical export

transport_effect

lowers Basolateral-to-apical flux exceeded absorptive flux and zosuquidar inhibited the apical efflux, so the step removes berberine from the cell.

transport_pool

the enterocyte interior Basolateral-to-apical flux exceeded absorptive flux and zosuquidar inhibited the apical efflux, so the step removes berberine from the cell.

Berberine: metabolism, nutrient connections and drug interactions (2026-09-17) · lines 233–244

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Polarized transporter-transfected MDCKII cells · source_derived_draft · unverified_draft

### berberine-abcb1-efflux OCT1/ABCB1 double-transfected cells transported berberine basolaterally to apically faster than single transfectants; zosuquidar inhibited apical efflux. Condition category: normal nutrient_topic: Berberine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An entry transporter and an exit pump can work in sequence. organism: Human OCT1, OCT2 and ABCB1 in engineered canine cells tissue_or_cell_type: Basolateral uptake and apical export experimental_model: Polarized transporter-transfected MDCKII cells limitations: Engineered system, not direct evidence for human oral bioavailability or a universal transport bottleneck. exposure: Berberine transport kinetics and transporter inhibition evidence_span: {"source_cache": "artifacts/berberine-research/18157518.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b", "start_char": 0, "end_char": 1918, "text_sha256": "34651ed2e9ce3c38b6042e616b5c36d932fe6f1099c627d1b5403b338eae7b2b"} [berberine-p18157518] Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). (2008). https://pubmed.ncbi.nlm.nih.gov/18157518/ DOI: 10.1007/s00210-007-0219-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake

exposure

Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice

limitations

Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Mouse and human transporter

plain_language

The drug and the vitamin compete for the same door.

primary_references

[metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

tissue_or_cell_type

Liver and intestine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 1243–1254

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake · source_derived_draft · unverified_draft

### metformin-metformin-thiamine-competition Metformin and the biguanide analogue phenformin competitively inhibited OCT1-mediated thiamine uptake. Condition category: nutrient_deficiency nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The drug and the vitamin compete for the same door. organism: Mouse and human transporter tissue_or_cell_type: Liver and intestine experimental_model: Oct1-knockout and human OCT1 transgenic mice, metabolomics and isotopic uptake limitations: Identifies thiamine as an endogenous OCT1 substrate and shows competitive inhibition by metformin. The steatosis phenotype is a mouse phenotype. exposure: Metformin and phenformin against thiamine uptake; acute metformin in wild-type mice evidence_span: {"source_cache": "artifacts/metformin-research/24961373.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70", "start_char": 0, "end_char": 1270, "text_sha256": "77be4a228b3d067ca1e7ba44e8148f5fbda7956a23b42fb8281e9faf451a0e70"} [metformin-p24961373] OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin. (2014). https://pubmed.ncbi.nlm.nih.gov/24961373/ DOI: 10.1073/pnas.1314939111

evidence_span

{"source_cache": "artifacts/metformin-research/25510240.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8eaf94237679ed7436f863e210d17b13a7219d064e46e7da915ed083c5b04c9", "start_char": 0, "end_char": 1355, "text_sha256": "f8eaf94237679ed7436f863e210d17b13a7219d064e46e7da915ed083c5b04c9"}

experimental_model

Case-control comparison of 251 metformin-intolerant and 1915 tolerant people in GoDARTS

exposure

Prescribed metformin, OCT1 genotype and co-prescribed OCT1 inhibitors

limitations

An association study. Intolerance is self-evidently multifactorial, and the proposed intestinal-concentration mechanism was not measured here.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human

plain_language

The transporter that controls where the drug goes is also linked to who cannot tolerate it.

primary_references

[metformin-p25510240] Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. (2015). https://pubmed.ncbi.nlm.nih.gov/25510240/ DOI: 10.2337/db14-1388

tissue_or_cell_type

Gastrointestinal tolerance

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 359–370

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Case-control comparison of 251 metformin-intolerant and 1915 tolerant people in GoDARTS · source_derived_draft · unverified_draft

### metformin-oct1-intolerance Carriage of two reduced-function OCT1 alleles was associated with metformin intolerance (odds ratio 2.41), rising to 4.13 in people also taking OCT1-inhibiting drugs. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The transporter that controls where the drug goes is also linked to who cannot tolerate it. organism: Human tissue_or_cell_type: Gastrointestinal tolerance experimental_model: Case-control comparison of 251 metformin-intolerant and 1915 tolerant people in GoDARTS limitations: An association study. Intolerance is self-evidently multifactorial, and the proposed intestinal-concentration mechanism was not measured here. exposure: Prescribed metformin, OCT1 genotype and co-prescribed OCT1 inhibitors evidence_span: {"source_cache": "artifacts/metformin-research/25510240.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8eaf94237679ed7436f863e210d17b13a7219d064e46e7da915ed083c5b04c9", "start_char": 0, "end_char": 1355, "text_sha256": "f8eaf94237679ed7436f863e210d17b13a7219d064e46e7da915ed083c5b04c9"} [metformin-p25510240] Association of Organic Cation Transporter 1 With Intolerance to Metformin in Type 2 Diabetes: A GoDARTS Study. (2015). https://pubmed.ncbi.nlm.nih.gov/25510240/ DOI: 10.2337/db14-1388

evidence_span

{"source_cache": "artifacts/metformin-research/33037045.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67", "start_char": 0, "end_char": 2296, "text_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67"}

experimental_model

Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling

exposure

Metformin and thiamine uptake kinetics; transmembrane-helix substitutions

limitations

A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human and mouse orthologues side by side

plain_language

Two helices carry the species difference in how tightly the drug binds.

primary_references

[metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

tissue_or_cell_type

Hepatic uptake

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 346–357

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling · source_derived_draft · unverified_draft

### metformin-oct1-tmh-determinant Simultaneous substitution of transmembrane helices TMH2 and TMH3 reversed the affinity for metformin in human-mouse chimeric OCT1. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Two helices carry the species difference in how tightly the drug binds. organism: Human and mouse orthologues side by side tissue_or_cell_type: Hepatic uptake experimental_model: Stably transfected HEK293 cells comparing human and mouse OCT1, with human-mouse chimeras and homology modelling limitations: A species comparison of transport affinity. It limits how far mouse OCT1 results can be read as human ones; it is not itself a human tissue measurement. exposure: Metformin and thiamine uptake kinetics; transmembrane-helix substitutions evidence_span: {"source_cache": "artifacts/metformin-research/33037045.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67", "start_char": 0, "end_char": 2296, "text_sha256": "861e39b20a78d5d85a01c5de0febda8bf1c400de4fa8ef1e6944707521604c67"} [metformin-p33037045] Differences in Metformin and Thiamine Uptake between Human and Mouse Organic Cation Transporter 1: Structural Determinants and Potential Consequences for Intrahepatic Concentrations. (2020). https://pubmed.ncbi.nlm.nih.gov/33037045/ DOI: 10.1124/dmd.120.000170

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"}

experimental_model

Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies

exposure

Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests

limitations

Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Mouse and human, stated per record

plain_language

People who carry a weaker version of the transporter responded less to the drug.

primary_references

[metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558

tissue_or_cell_type

Hepatocytes and whole body

trigger_kind

machinery_impairment Imported condition classification; unverified.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 164–175

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies · source_derived_draft · unverified_draft

### metformin-oct1-variants-response In clinical studies the effects of metformin in glucose tolerance tests were significantly smaller in people carrying reduced-function OCT1 polymorphisms. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: People who carry a weaker version of the transporter responded less to the drug. organism: Mouse and human, stated per record tissue_or_cell_type: Hepatocytes and whole body experimental_model: Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies limitations: Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing. exposure: Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests evidence_span: {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"} [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"}

experimental_model

Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies

exposure

Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests

limitations

Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Mouse and human, stated per record

plain_language

A transporter can look normal on a test substrate and still handle this drug poorly.

primary_references

[metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558

tissue_or_cell_type

Hepatocytes and whole body

trigger_kind

machinery_impairment Imported condition classification; unverified.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 125–136

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies · source_derived_draft · unverified_draft

### metformin-oct1-variants-uptake Seven non-synonymous OCT1 polymorphisms showed reduced metformin uptake, including OCT1-420del, which has normal activity for model substrates. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: A transporter can look normal on a test substrate and still handle this drug poorly. organism: Mouse and human, stated per record tissue_or_cell_type: Hepatocytes and whole body experimental_model: Oct1-knockout mouse hepatocytes and mice, human variant uptake assays, and human glucose-tolerance studies limitations: Pharmacogenetic association with drug response, not proof that OCT1 genotype should guide prescribing. exposure: Metformin in Oct1-deficient mice; seven non-synonymous human OCT1 variants; clinical glucose tolerance tests evidence_span: {"source_cache": "artifacts/metformin-research/17476361.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1", "start_char": 0, "end_char": 1361, "text_sha256": "e8d05affc6b49c7273e21804d2ad9092ca826c8d81431ee093c6215f18f0bce1"} [metformin-p17476361] Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. (2007). https://pubmed.ncbi.nlm.nih.gov/17476361/ DOI: 10.1172/jci30558

evidence_span

{"source_cache": "artifacts/metformin-research/16272756.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9da4317752d37da62129139affd33016e879d367c4cf58cfefb9200c663fe4ed", "start_char": 0, "end_char": 1284, "text_sha256": "9da4317752d37da62129139affd33016e879d367c4cf58cfefb9200c663fe4ed"}

experimental_model

Human and rat transporter cDNA transfection into HEK293 cells with rat tissue distribution

exposure

Metformin uptake across five renal organic ion transporters and tissue accumulation in male rats

limitations

Relative capacities are transfection-dependent; the study itself notes that plasmid amount changes the apparent kinetics.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Human and rat transporters; rat in vivo

plain_language

The kidney transporter moves far more of the drug than the liver one does.

primary_references

[metformin-p16272756] Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. (2005). https://pubmed.ncbi.nlm.nih.gov/16272756/ DOI: 10.2133/dmpk.20.379

tissue_or_cell_type

Kidney and liver

transport_effect

raises A transfected-cell capacity comparison, measured as metformin carried into the cell.

transport_pool

the expressing cell A transfected-cell capacity comparison, measured as metformin carried into the cell.

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 177–188

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and rat transporter cDNA transfection into HEK293 cells with rat tissue distribution · source_derived_draft · unverified_draft

### metformin-oct2-capacity Human and rat OCT2 had roughly 10-fold and 100-fold greater capacity to transport metformin than OCT1 in the transfected-cell comparison. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The kidney transporter moves far more of the drug than the liver one does. organism: Human and rat transporters; rat in vivo tissue_or_cell_type: Kidney and liver experimental_model: Human and rat transporter cDNA transfection into HEK293 cells with rat tissue distribution limitations: Relative capacities are transfection-dependent; the study itself notes that plasmid amount changes the apparent kinetics. exposure: Metformin uptake across five renal organic ion transporters and tissue accumulation in male rats evidence_span: {"source_cache": "artifacts/metformin-research/16272756.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9da4317752d37da62129139affd33016e879d367c4cf58cfefb9200c663fe4ed", "start_char": 0, "end_char": 1284, "text_sha256": "9da4317752d37da62129139affd33016e879d367c4cf58cfefb9200c663fe4ed"} [metformin-p16272756] Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1. (2005). https://pubmed.ncbi.nlm.nih.gov/16272756/ DOI: 10.2133/dmpk.20.379