Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action.

Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. Research Abstract Details 

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Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. Abstract Text:

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.

Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. Publishing Authors By Initials

For similar genetic phenomena: variation (genetics) research abstracts see: genetic phenomena: variation (genetics) research

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Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of clinical investigation

VOLUME: 117

Page Numbers: 1422-31

Journal Abbreviation:

ISSN: 0021-9738

DAY: 3

MONTH: May

YEAR: 2007

Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. Keywords Mesh Terms:

KEYWORDS: Variation (Genetics)

MESH TERMS: physiology

Chemical & Substance for Abstract: Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. Information

Substance Name: Metformin

Registry Number: 657-24-9

Grant and Affiliation Information for Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action.

AFFILIATION: Department of Biopharmaceutical Sciences, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: P30 DK 26743

ACRONYM: DK

MEDLINETA: J Clin Invest

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