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The Synergistic Effects of Pioglitazone on the Glucose-Lowering Action of Metformin in Relation to OCT1 and Gluts m-RNA Expression in Healthy Volunteer | Abstract
ISSN: 2167-065X

Clinical Pharmacology & Biopharmaceutics
Open Access

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Research Article

The Synergistic Effects of Pioglitazone on the Glucose-Lowering Action of Metformin in Relation to OCT1 and Gluts m-RNA Expression in Healthy Volunteer

Sung K Cho1,2*
1Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea
2Armed Forces Medical Research Institute, Daejeon, Korea
Corresponding Author : Sung Kweon Cho
Armed Forces Medical Research Institute
90 bun, Jaunro, Yuseong-gu
Daejeon 305-878, Korea
Tel: +82-42-878- 4868
E-mail: [email protected]
Received December 12, 2014; Accepted January 07, 2015; Published January 09, 2015
Citation: Cho SK (2015) The Synergistic Effects of Pioglitazone on the Glucose-Lowering Action of Metformin in Relation to OCT1 and Gluts m-RNA Expression in Healthy Volunteer. Clin Pharmacol Biopharm 3:129. doi:10.4172/2167-065X.1000129
Copyright: © 2015 Cho SK. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: Organic Cation Transporter 1 (OCT1) plays a key role in the disposition of metformin in hepatocytes; a recent non-clinical study reported that the peroxisome-proliferator activated receptor γ agonist pioglitazone increased the expression of Slc22a1 (Oct1) by 3.1-fold as well as its transporting function. We therefore evaluated the effect of pioglitazone on the glucose-lowering effect of metformin in 15 human participants using the Oral Glucose Tolerance Test (OGTT) and measuring the mRNA levels of OCT1, as well as those of Glucose Transporter 1 (GLUT 1) and GLUT4, which are also important in glucose utilization, in peripheral blood cells. Research design and methods: The glucose-lowering effects of metformin were evaluated by the OGTT before and after metformin treatment on Days 1 and 2 of the study and again on Days 18 and 19 after a 14-day course of pioglitazone 30 mg/day. Differences in maximum glucose levels (ΔGmax) and the areas under the glucose-time curve during the first 60 min after glucose ingestion (ΔAUCgluc60) and the entire 180-min test (ΔAUCgluc) caused by metformin treatment were determined before and after pioglitazone administration. Results: Pioglitazone increased ΔGmax by 50.0% (P=0.021), ΔAUCgluc60 by 88.1% (P=0.020), and ΔAUCgluc by 266%. Pioglitazone did not increase OCT1 and GLUT1 mRNA levels in peripheral blood cells. Conclusion: OCT1 induction plays a limited role in the synergistic effect of pioglitazone on the glucose-lowering activity of metformin. However, this synergistic effect lasted 3 days after pioglitazone treatment ended, which warrants further clinical investigation.

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