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Hindi 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: wontan2000@gmail.com |
| 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.
