Oleanolic acid enhances insulin secretion in pancreatic β-cells

Teodoro, Tracy; Zhang, Liling; Alexander, Todd; Yue, Jessica; Vranic, Mladen; Volchuk, Allen

doi:10.1016/j.febslet.2008.03.026

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Volume 582, Issue 9 , Pages 1375-1380, 16 April 2008

Oleanolic acid enhances insulin secretion in pancreatic β-cells

Edited by Robert Barouki

Tracy Teodoro
- Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, 101 College Street, TMDT 10-707, Toronto, ON, Canada M5G1L7
- Department of Biochemistry, University of Toronto, Canada
Liling Zhang
- Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, 101 College Street, TMDT 10-707, Toronto, ON, Canada M5G1L7
Todd Alexander
- The Hospital for Sick Children, Toronto, Canada
Jessica Yue
- Department of Physiology, University of Toronto, Canada
Mladen Vranic
- Department of Physiology, University of Toronto, Canada
Allen Volchuk
- Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, 101 College Street, TMDT 10-707, Toronto, ON, Canada M5G1L7
- Department of Biochemistry, University of Toronto, Canada
- Department of Physiology, University of Toronto, Canada
- Corresponding author. Address: Division of Cell and Molecular Biology, Toronto General Research Institute, University Health Network, 101 College Street, TMDT 10-707, Toronto, ON, Canada M5G1L7. Fax: +1 416 978 4108.

Received 11 October 2007; received in revised form 20 February 2008; accepted 16 March 2008. published online 25 March 2008.

Abstract

We investigated the effect of oleanolic acid, a plant-derived triterpenoid, on insulin secretion and content in pancreatic β-cells and rat islets. Oleanolic acid significantly enhanced insulin secretion at basal and stimulatory glucose concentrations in INS-1 832/13 cells and enhanced acute glucose-stimulated insulin secretion in isolated rat islets. In the cell line the effects of oleanolic acid on insulin secretion were comparable to that of the sulfonylurea tolbutamide at basal glucose levels and with the incretin mimetic Exendin-4 under glucose-stimulated conditions, yet neither Ca²⁺ nor cAMP rose in response to oleanolic acid. Chronic treatment with oleanolic acid increased total cellular insulin protein and mRNA levels. These effects may contribute to the anti-diabetic properties of this natural product.

Keywords: Pancreatic beta-cell, Insulin secretion, Oleanolic acid, Insulin biosynthesis