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Article ; Online: 3-Iodothyronamine (T(1)AM): a new chapter of thyroid hormone endocrinology?

Ianculescu, Alexandra G / Scanlan, Thomas S

2010 Volume 6, Issue 8, Page(s) 1338–1344

Abstract: 3-Iodothyronamine (T(1)AM) is an endogenous thyroid hormone derivative with distinct biological effects that are largely opposite those of thyroid hormone. Administration of T(1)AM to rodents results in rapid and profound reduction in body temperature, ... ...

Abstract	3-Iodothyronamine (T(1)AM) is an endogenous thyroid hormone derivative with distinct biological effects that are largely opposite those of thyroid hormone. Administration of T(1)AM to rodents results in rapid and profound reduction in body temperature, heart rate, and metabolism. The structural similarities between thyroxine, T(1)AM, and monoamine neurotransmitters suggest an intriguing role for T(1)AM as both a neuromodulator and a hormone-like molecule that may constitute a part of thyroid hormone action. Several recent studies into its molecular mechanisms of action have shown that T(1)AM can target extracellular receptors such as the trace amine-associated receptors and the alpha(2A) adrenergic receptor, modulate the membrane transport of neurotransmitters, and serve as a substrate of specific membrane transport cellular uptake machinery. This review discusses recent T(1)AM studies, focusing on both the observed in vivo effects of T(1)AM administration and its actions at the molecular level.
MeSH term(s)	Animals ; Endocrine System/drug effects ; Endocrine System/metabolism ; Endocrine System/physiology ; Endocrinology/trends ; Humans ; Models, Biological ; Thyroid Hormones/physiology ; Thyronines/metabolism ; Thyronines/pharmacology ; Thyronines/physiology ; Thyronines/therapeutic use
Chemical Substances	3-iodothyronamine ; Thyroid Hormones ; Thyronines
Language	English
Publishing date	2010-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2188635-0
ISSN	1742-2051 ; 1742-206X
ISSN (online)	1742-2051
ISSN	1742-206X
DOI	10.1039/b926583j
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Article ; Online: Identification and characterization of 3-iodothyronamine intracellular transport.

Ianculescu, Alexandra G / Giacomini, Kathleen M / Scanlan, Thomas S

Endocrinology

2008 Volume 150, Issue 4, Page(s) 1991–1999

Abstract: 3-Iodothyronamine (T(1)AM) is a naturally occurring thyroid hormone metabolite with distinct biological effects that are opposite those of thyroid hormone. The known molecular targets of T(1)AM include both plasma membrane and intracellular proteins, ... ...

Abstract	3-Iodothyronamine (T(1)AM) is a naturally occurring thyroid hormone metabolite with distinct biological effects that are opposite those of thyroid hormone. The known molecular targets of T(1)AM include both plasma membrane and intracellular proteins, suggesting that intracellular transport of T(1)AM may be an important component of its action, although no uptake mechanism has yet been described. Using various human cell lines, we show that, indeed, cellular uptake of T(1)AM occurs in multiple cell types and that this process involves specific, saturable, and inhibitable transport mechanisms. These mechanisms are sodium and chloride independent, pH dependent, thyronamine specific, and do not involve the likely candidate transporters of other monoamines, organic cations, or thyroid hormones. A large-scale RNA interference screen targeting the entire solute carrier superfamily of transporter genes reveals that the transport of T(1)AM into cells involves multiple transporters, and we identify eight transporters that may contribute to the uptake of T(1)AM in HeLa cells. This type of transporter small interfering RNA screening approach can be used in general to identify the constellation of transporters that participate in the intracellular disposition of compounds.
MeSH term(s)	1-Methyl-4-phenylpyridinium/metabolism ; Acyclovir/metabolism ; Biological Transport/genetics ; Biological Transport/physiology ; Carnitine/metabolism ; Cell Line ; Equilibrative-Nucleoside Transporter 2/genetics ; Equilibrative-Nucleoside Transporter 2/metabolism ; Estrone/analogs & derivatives ; Estrone/metabolism ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/metabolism ; Monocarboxylic Acid Transporters/genetics ; Monocarboxylic Acid Transporters/metabolism ; Organic Anion Transport Protein 1/genetics ; Organic Anion Transport Protein 1/metabolism ; Organic Anion Transporters, Sodium-Independent/genetics ; Organic Anion Transporters, Sodium-Independent/metabolism ; Organic Cation Transporter 1/genetics ; Organic Cation Transporter 1/metabolism ; RNA Interference ; RNA, Small Interfering/genetics ; RNA, Small Interfering/physiology ; Symporters ; Tetraethylammonium/metabolism ; Thyronines/metabolism
Chemical Substances	3-iodothyronamine ; Equilibrative-Nucleoside Transporter 2 ; Membrane Transport Proteins ; Monocarboxylic Acid Transporters ; Organic Anion Transport Protein 1 ; Organic Anion Transporters, Sodium-Independent ; Organic Cation Transporter 1 ; RNA, Small Interfering ; SLC16A2 protein, human ; Symporters ; Thyronines ; organic anion transport protein 3 ; Estrone (2DI9HA706A) ; thyronamine (500-78-7) ; Tetraethylammonium (66-40-0) ; estrone sulfate (QTL48N278K) ; 1-Methyl-4-phenylpyridinium (R865A5OY8J) ; Carnitine (S7UI8SM58A) ; Acyclovir (X4HES1O11F)
Language	English
Publishing date	2008-12-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2008-1339
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Article ; Online: Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine.

Ianculescu, Alexandra G / Friesema, Edith C H / Visser, Theo J / Giacomini, Kathleen M / Scanlan, Thomas S

Molecular bioSystems

2010 Volume 6, Issue 8, Page(s) 1403–1410

Abstract: Thyroid hormone transporters are responsible for the cellular uptake of thyroid hormones, which is a prerequisite for their subsequent metabolism and action at nuclear thyroid hormone receptors. A recently discovered thyroid hormone derivative, 3- ... ...

Abstract	Thyroid hormone transporters are responsible for the cellular uptake of thyroid hormones, which is a prerequisite for their subsequent metabolism and action at nuclear thyroid hormone receptors. A recently discovered thyroid hormone derivative, 3-iodothyronamine (T(1)AM), has distinct biological effects that are opposite those of thyroid hormone. Here we investigate the effects of T(1)AM on thyroid hormone transporters using COS-1 cells transfected with the multispecific organic anion transporting polypeptides (OATPs) 1A2, 1B3, and 1C1, as well as the specific thyroid hormone transporters MCT8 and MCT10, and show that T(1)AM displays differential inhibition of T(3) and T(4) cellular uptake by these transporters. T(1)AM inhibits T(3) and T(4) transport by OATP1A2 with IC(50) values of 0.27 and 2.1 microM, respectively. T(4) transport by OATP1C1, which is thought to play a key role in thyroid hormone transport across the blood-brain barrier, is inhibited by T(1)AM with an IC(50) of 4.8 microM. T(1)AM also inhibits both T(3) and T(4) uptake via MCT8, the most specific thyroid hormone transporter identified to date, with IC(50) values of 95 and 31 microM, respectively. By contrast, T(1)AM has no effect on thyroid hormone transport by OATP1B3 and MCT10. Given that OATP1A2, OATP1C1, and MCT8 are all present in the brain, T(1)AM may play an important role in modulating thyroid hormone delivery and activity in specific target regions in the central nervous system.
MeSH term(s)	Amino Acid Transport Systems, Neutral/genetics ; Amino Acid Transport Systems, Neutral/metabolism ; Animals ; Biological Transport/drug effects ; COS Cells ; Chlorocebus aethiops ; Down-Regulation/drug effects ; Humans ; Inhibitory Concentration 50 ; Monocarboxylic Acid Transporters/genetics ; Monocarboxylic Acid Transporters/metabolism ; Organic Anion Transporters/antagonists & inhibitors ; Organic Anion Transporters/genetics ; Organic Anion Transporters/metabolism ; Substrate Specificity ; Symporters ; Thyroid Hormones/metabolism ; Thyroid Hormones/pharmacokinetics ; Thyronines/pharmacology ; Transfection
Chemical Substances	3-iodothyronamine ; Amino Acid Transport Systems, Neutral ; Monocarboxylic Acid Transporters ; Organic Anion Transporters ; SLC16A10 protein, human ; SLC16A2 protein, human ; SLCO1A2 protein, human ; SLCO1C1 protein, human ; Symporters ; Thyroid Hormones ; Thyronines
Language	English
Publishing date	2010-03-31
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2188635-0
ISSN	1742-2051 ; 1742-206X
ISSN (online)	1742-2051
ISSN	1742-206X
DOI	10.1039/b926588k
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Article ; Online: Role of the copper transporter, CTR1, in platinum-induced ototoxicity.

More, Swati S / Akil, Omar / Ianculescu, Alexandra G / Geier, Ethan G / Lustig, Lawrence R / Giacomini, Kathleen M

The Journal of neuroscience : the official journal of the Society for Neuroscience

2010 Volume 30, Issue 28, Page(s) 9500–9509

Abstract: The goal of this study was to determine the role of an influx copper transporter, CTR1, in the ototoxicity induced by cisplatin, a potent anticancer platinum analog used in the treatment of a variety of solid tumors. As determined through reverse ... ...

Abstract	The goal of this study was to determine the role of an influx copper transporter, CTR1, in the ototoxicity induced by cisplatin, a potent anticancer platinum analog used in the treatment of a variety of solid tumors. As determined through reverse transcriptase-PCR (RT-PCR), quantitative RT-PCR, Western blot, and immunohistochemistry, mouse CTR1 (Ctr1) was found to be abundantly expressed and highly localized at the primary sites of cisplatin toxicity in the inner ear, mainly outer hair cells (OHCs), inner hair cells, stria vascularis, spiral ganglia, and surrounding nerves in the mouse cochlea. A CTR1 substrate, copper sulfate, decreased the uptake and cytotoxicity of cisplatin in HEI-OC1, a cell line that expresses many molecular markers reminiscent of OHCs. Small interfering RNA-mediated knockdown of Ctr1 in this cell line caused a corresponding decrease in cisplatin uptake. In mice, intratympanic administration of copper sulfate 30 min before intraperitoneal administration of cisplatin was found to prevent hearing loss at click stimulus and 8, 16, and 32 kHz frequencies. To date, the utility of cisplatin remains severely limited because of its ototoxic effects. The studies described in this report suggest that cisplatin-induced ototoxicity and cochlear uptake can be modulated by administration of a CTR1 inhibitor, copper sulfate. The possibility of local administration of CTR1 inhibitors during cisplatin therapy as a means of otoprotection is thereby raised.
MeSH term(s)	Acoustic Stimulation ; Animals ; Blotting, Western ; Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Cell Count ; Cell Line ; Cisplatin/pharmacology ; Cochlea/drug effects ; Cochlea/metabolism ; Copper Transporter 1 ; Hair Cells, Auditory/drug effects ; Hair Cells, Auditory/metabolism ; Hearing Loss/chemically induced ; Hearing Loss/metabolism ; Humans ; Immunohistochemistry ; Mice ; Reverse Transcriptase Polymerase Chain Reaction
Chemical Substances	Cation Transport Proteins ; Copper Transporter 1 ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2010-07-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1544-10.2010
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Article ; Online: 3-Monoiodothyronamine: the rationale for its action as an endogenous adrenergic-blocking neuromodulator.

Gompf, Heinrich S / Greenberg, Joel H / Aston-Jones, Gary / Ianculescu, Alexandra G / Scanlan, Tom S / Dratman, Mary B

Brain research

2010 Volume 1351, Page(s) 130–140

Abstract: The investigations reported here were designed to gain insights into the role of 3-monoiodothyronamine (T1AM) in the brain, where the amine was originally identified and characterized. Extensive deiodinase studies indicated that T1AM was derived from the ...

Abstract	The investigations reported here were designed to gain insights into the role of 3-monoiodothyronamine (T1AM) in the brain, where the amine was originally identified and characterized. Extensive deiodinase studies indicated that T1AM was derived from the T4 metabolite, reverse triiodothyronine (revT3), while functional studies provided well-confirmed evidence that T1AM has strong adrenergic-blocking effects. Because a state of adrenergic overactivity prevails when triiodothyronine (T3) concentrations become excessive, the possibility that T3's metabolic partner, revT3, might give rise to an antagonist of those T3 actions was thought to be reasonable. All T1AM studies thus far have required use of pharmacological doses. Therefore we considered that choosing a physiological site of action was a priority and focused on the locus coeruleus (LC), the major noradrenergic control center in the brain. Site-directed injections of T1AM into the LC elicited a significant, dose-dependent neuronal firing rate change in a subset of adrenergic neurons with an EC(50)=2.7 microM, a dose well within the physiological range. Further evidence for its physiological actions came from autoradiographic images obtained following intravenous carrier-free (125)I-labeled T1AM injection. These showed that the amine bound with high affinity to the LC and to other selected brain nuclei, each of which is both an LC target and a known T3 binding site. This new evidence points to a physiological role for T1AM as an endogenous adrenergic-blocking neuromodulator in the central noradrenergic system.
MeSH term(s)	Action Potentials/drug effects ; Action Potentials/physiology ; Adrenergic beta-Antagonists/metabolism ; Adrenergic beta-Antagonists/pharmacology ; Animals ; Dose-Response Relationship, Drug ; Locus Coeruleus/drug effects ; Locus Coeruleus/metabolism ; Male ; Neurotransmitter Agents/pharmacology ; Neurotransmitter Agents/physiology ; Rats ; Rats, Sprague-Dawley ; Thyronines/pharmacology ; Thyronines/physiology ; Triiodothyronine/pharmacology ; Triiodothyronine/physiology
Chemical Substances	Adrenergic beta-Antagonists ; Neurotransmitter Agents ; Thyronines ; Triiodothyronine (06LU7C9H1V) ; thyronamine (500-78-7)
Language	English
Publishing date	2010-07-23
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2010.06.067
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Article: A mathematical model of the impact of infused targeted cytotoxic agents on brain tumours: implications for detection, design and delivery.

Wein, Lawrence M / Wu, Joseph T / Ianculescu, Alexandra G / Puri, Raj K

Cell proliferation

2002 Volume 35, Issue 6, Page(s) 343–361

Abstract: ... cytotoxic agent (e.g. IL-4-PE, a cytotoxin comprised of IL-4 and a mutated form of Pseudomonas exotoxin ...

Abstract	Motivated by the recent development of highly specific agents for brain tumours, we develop a mathematical model of the spatio-temporal dynamics of a brain tumour that receives an infusion of a highly specific cytotoxic agent (e.g. IL-4-PE, a cytotoxin comprised of IL-4 and a mutated form of Pseudomonas exotoxin). We derive an approximate but accurate mathematical formula for the tumour cure probability in terms of the tumour characteristics (size at time of detection, proliferation rate, diffusion coefficient), drug design (killing rate, loss rate and convection constants for tumour and tissue), and drug delivery (infusion rate, infusion duration). Our results suggest that high specificity is necessary but not sufficient to cure malignant gliomas; a nondispersed spatial profile of pretreatment tumour cells and/or good drug penetration are also required. The most important levers to improve tumour cure appear to be earlier detection, higher infusion rate, lower drug clearance rate and better convection into tumour, but not tissue. In contrast, the tumour cure probability is less sensitive to a longer infusion duration and enhancements in drug potency and drug specificity.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/toxicity ; Brain Neoplasms/drug therapy ; Brain Neoplasms/pathology ; Cell Division/drug effects ; Drug Delivery Systems/methods ; Drug Design ; Exotoxins/administration & dosage ; Exotoxins/toxicity ; Glioma/drug therapy ; Glioma/pathology ; Humans ; Infusions, Intralesional ; Interleukin-4/administration & dosage ; Interleukin-4/toxicity ; Models, Theoretical ; Recombinant Fusion Proteins/administration & dosage ; Recombinant Fusion Proteins/toxicity
Chemical Substances	Antineoplastic Agents ; Exotoxins ; IL-4-PE40 protein, recombinant ; Recombinant Fusion Proteins ; Interleukin-4 (207137-56-2)
Language	English
Publishing date	2002-12
Publishing country	England
Document type	Journal Article
ZDB-ID	1064202-x
ISSN	1365-2184 ; 0960-7722 ; 0008-8730
ISSN (online)	1365-2184
ISSN	0960-7722 ; 0008-8730
DOI	10.1046/j.1365-2184.2002.00246.x
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Article: A conserved RING finger protein required for histone H2B monoubiquitination and cell size control.

Hwang, William W / Venkatasubrahmanyam, Shivkumar / Ianculescu, Alexandra G / Tong, Amy / Boone, Charles / Madhani, Hiten D

Molecular cell

2002 Volume 11, Issue 1, Page(s) 261–266

Abstract: Monoubiquitination of histone H2B is required for methylation of histone H3 on lysine 4 (K4), a modification associated with active chromatin. The identity of the cognate ubiquitin ligase is unknown. We identify Bre1 as an evolutionarily conserved RING ... ...

Abstract	Monoubiquitination of histone H2B is required for methylation of histone H3 on lysine 4 (K4), a modification associated with active chromatin. The identity of the cognate ubiquitin ligase is unknown. We identify Bre1 as an evolutionarily conserved RING finger protein required in vivo for both H2B ubiquitination and H3 K4 methylation. The RING domain of Bre1 is essential for both of these modifications as is Lge1 (Large 1), a protein required for cell size control that copurifies with Bre1. In cells lacking the euchromatin-associated histone variant H2A.Z, BRE1, RAD6, and LGE1 are each essential for cell viability, supporting redundant functions for H2B ubiquitination and H2A substitution in the formation of active chromatin. Notably, analysis of mutants demonstrates a function for Bre1/Lge1-dependent H2B monoubiquitination in the control of cell size.
MeSH term(s)	Amino Acid Sequence ; Animals ; Cell Size ; Histones/metabolism ; Humans ; Macromolecular Substances ; Methylation ; Molecular Sequence Data ; Protein Structure, Tertiary ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/chemistry ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Sequence Alignment ; Ubiquitin/metabolism
Chemical Substances	Bre1 protein, S cerevisiae ; Histones ; Macromolecular Substances ; Saccharomyces cerevisiae Proteins ; Ubiquitin
Language	English
Publishing date	2002-11-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1415236-8
ISSN	1097-4164 ; 1097-2765
ISSN (online)	1097-4164
ISSN	1097-2765
DOI	10.1016/s1097-2765(02)00826-2
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Article ; Online: Evidence for a homodimeric structure of human monocarboxylate transporter 8.

Visser, W Edward / Philp, Nancy J / van Dijk, Thamar B / Klootwijk, Wim / Friesema, Edith C H / Jansen, Jurgen / Beesley, Philip W / Ianculescu, Alexandra G / Visser, Theo J

Endocrinology

2009 Volume 150, Issue 11, Page(s) 5163–5170

Abstract: The human monocarboxylate transporter 8 (hMCT8) protein mediates transport of thyroid hormone across the plasma membrane. Association of hMCT8 mutations with severe psychomotor retardation and disturbed thyroid hormone levels has established its ... ...

Abstract	The human monocarboxylate transporter 8 (hMCT8) protein mediates transport of thyroid hormone across the plasma membrane. Association of hMCT8 mutations with severe psychomotor retardation and disturbed thyroid hormone levels has established its physiological relevance, but little is still known about the basic properties of hMCT8. In this study we present evidence that hMCT8 does not form heterodimers with the ancillary proteins basigin, embigin, or neuroplastin, unlike other MCTs. In contrast, it is suggested that MCT8 exists as monomer and homodimer in transiently and stably transfected cells. Apparently hMCT8 forms stable dimers because the complex is resistant to denaturing conditions and dithiothreitol. Cotransfection of wild-type hMCT8 with a mutant lacking amino acids 267-360 resulted in formation of homo-and heterodimers of the variants, indicating that transmembrane domains 4-6 are not involved in the dimerization process. Furthermore, we explored the structural and functional role of the 10 Cys residues in hMCT8. All possible Cys>Ala mutants did not behave differently from wild-type hMCT8 in protein expression, cross-linking experiments with HgCl(2) and transport function. Our findings indicate that individual Cys residues are not important for the function of hMCT8 or suggest that hMCT8 has other yet-undiscovered functions in which cysteines play an essential role.
MeSH term(s)	Amino Acid Sequence ; Animals ; COS Cells ; Cell Line ; Chlorocebus aethiops ; Humans ; Mice ; Molecular Sequence Data ; Monocarboxylic Acid Transporters/chemistry ; Monocarboxylic Acid Transporters/genetics ; Monocarboxylic Acid Transporters/metabolism ; Mutation ; Protein Multimerization ; Protein Structure, Tertiary ; Symporters ; Thyroid Hormones/metabolism
Chemical Substances	Monocarboxylic Acid Transporters ; SLC16A2 protein, human ; Symporters ; Thyroid Hormones
Language	English
Publishing date	2009-09-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	427856-2
ISSN	1945-7170 ; 0013-7227
ISSN (online)	1945-7170
ISSN	0013-7227
DOI	10.1210/en.2009-0699
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Article: Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action.

Shu, Yan / Sheardown, Steven A / Brown, Chaline / Owen, Ryan P / Zhang, Shuzhong / Castro, Richard A / Ianculescu, Alexandra G / Yue, Lin / Lo, Joan C / Burchard, Esteban G / Brett, Claire M / Giacomini, Kathleen M

The Journal of clinical investigation

2007 Volume 117, Issue 5, Page(s) 1422–1431

Abstract: Metformin is among the most widely prescribed drugs for the treatment of type 2 diabetes. Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation ... ...

Abstract	Metformin is among the most widely prescribed drugs for the treatment of type 2 diabetes. Organic cation transporter 1 (OCT1) plays a role in the hepatic uptake of metformin, but its role in the therapeutic effects of the drug, which involve activation of AMP-activated protein kinase (AMPK), is unknown. Recent studies have shown that human OCT1 is highly polymorphic. We investigated whether OCT1 plays a role in the action of metformin and whether individuals with OCT1 polymorphisms have reduced response to the drug. In mouse hepatocytes, deletion of Oct1 resulted in a reduction in the effects of metformin on AMPK phosphorylation and gluconeogenesis. In Oct1-deficient mice the glucose-lowering effects of metformin were completely abolished. Seven nonsynonymous polymorphisms of OCT1 that exhibited reduced uptake of metformin were identified. Notably, OCT1-420del (allele frequency of about 20% in white Americans), previously shown to have normal activity for model substrates, had reduced activity for metformin. In clinical studies, the effects of metformin in glucose tolerance tests were significantly lower in individuals carrying reduced function polymorphisms of OCT1. Collectively, the data indicate that OCT1 is important for metformin therapeutic action and that genetic variation in OCT1 may contribute to variation in response to the drug.
MeSH term(s)	3T3-L1 Cells ; Animals ; Cell Line ; Clone Cells ; Female ; Genetic Variation/physiology ; Humans ; Hypoglycemic Agents/antagonists & inhibitors ; Hypoglycemic Agents/pharmacology ; Male ; Metformin/antagonists & inhibitors ; Metformin/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Organic Cation Transporter 1/genetics ; Organic Cation Transporter 1/physiology ; Polymorphism, Genetic
Chemical Substances	Hypoglycemic Agents ; Organic Cation Transporter 1 ; Metformin (9100L32L2N)
Language	English
Publishing date	2007-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI30558
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