OATP1B3 Is Expressed in Pancreatic β-Islet Cells and Enhances the Insulinotropic Effect of the Sulfonylurea Derivative Glibenclamide

  1. Werner Siegmund4
  1. 1Biopharmacy, Department of Pharmaceutical Sciences, University Basel, Basel, Switzerland
  2. 2Department of Pharmacology, Center of Drug Absorption and Transport, University Medicine Greifswald, Greifswald, Germany
  3. 3Department of Clinical Pharmacology, University of Western Ontario, London, Ontario, Canada
  4. 4Medical Faculty, University of Göttingen, Göttingen, Germany
  5. 5Department of Clinical Pharmacology, Center of Drug Absorption and Transport, University Medicine Greifswald, Greifswald, Germany
  1. Corresponding author: Henriette E. Meyer zu Schwabedissen, h.meyerzuschwabedissen{at}


Organic anion transporting polypeptide OATP1B3 is a membrane-bound drug transporter that facilitates cellular entry of a variety of substrates. Most of the previous studies focused on its hepatic expression and function in hepatic drug elimination. In this study, we report expression of OATP1B3 in human pancreatic tissue, with the abundance of the transporter localized in the islets of Langerhans. Transport studies using OATP1B3-overexpressing MDCKII cells revealed significant inhibition of the cellular uptake of the known substrate cholecystokinin-8 in the presence of the insulinotropic antidiabetes compounds tolbutamide, glibenclamide, glimepiride, and nateglinide and identified glibenclamide as a novel substrate of OATP1B3. Sulfonylurea derivatives exert their insulinotropic effect by binding to the SUR1 subunit of the KATP channels inducing insulin secretion in β-cells. Here, we show that transient overexpression of human OATP1B3 in a murine β-cell line (MIN6)—which exhibits glucose and glibenclamide-sensitive insulin secretion—significantly enhances the insulinotropic effect of glibenclamide without affecting glucose-stimulated insulin secretion. Taken together, our data provide evidence that the drug transporter OATP1B3 functions as a determinant of the insulinotropic effect of glibenclamide on the tissue level. Changes in transport activity based on drug-drug interactions or genetic variability may therefore influence glibenclamide efficacy.


  • Received June 27, 2013.
  • Accepted October 14, 2013.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

| Table of Contents