Effects of Extra Virgin Olive Oil Polyphenols on Pancreatic Beta-Cell Function and Survival

Abstract

Extra virgin olive oil (EVOO) is one of the major components of the Mediterranean diet and is appreciated worldwide because of its nutritional benefits in metabolic diseases, including type 2 diabetes. In addition to high levels of fatty acids, EVOO contains significant amounts of micronutrients such as polyphenolic compounds that may positively influence the metabolic status. In this study, we have evaluated the effects of such EVOO polyphenolic compounds on beta-cell function and survival. INS-1E cells were exposed to different doses (10-50-100 microM) of the main polyphenols of EVOO for 24 h. Under these conditions, glucose-stimulated insulin secretion (GSIS), insulin content, proinsulin mRNA expression and cellular apoptosis were evaluated. At the concentration of 10 microM, which is closest to that in EVOO, hydroxytyrosol, tyrosol and apigenin augmented proinsulin mRNA levels and insulin content; moreover, apigenin and luteolin enhanced GSIS. On the other hand, vanillic acid and vanillin were pro-apoptotic for beta-cells, even if they increased GSIS. Finally, ferulic and sinapic acids significantly worsened GSIS. Furthermore, although most of the polyphenol compounds at the concentration of 50 microM did not induce apoptosis, some of them (e.g., caffeic, vanillic and ferulic acids) caused a marked reduction in proinsulin gene expression. At the concentration of 100 microM, most polyphenolic compounds caused a reduction in proinsulin mRNA levels and enhanced apoptosis. In conclusion, this study, comparing for the first time the effects of the main polyphenols contained in EVOO, shows that, at low concentrations, hydroxytyrosol, tyrosol, luteolin and apigenin exert positive effects on both the function and survival of beta-cells, suggesting that EVOO enriched with these compounds may improve insulin secretion and promote glycemic control in type 2 diabetic patients. Disclosure A. Natalicchio: None. R. Spagnuolo: None. N. Marrano: None. G. Biondi: None. L. Dipaola: None. A. Cignarelli: Advisory Panel; Self; Aegerion Pharmaceuticals. Consultant; Self; Roche Diagnostics Corporation, Eli Lilly and Company. S. Perrini: None. L. Laviola: Advisory Panel; Self; AstraZeneca, Animas Corporation. Speaker's Bureau; Self; A. Menarini Diagnostics. Advisory Panel; Self; Boehringer Ingelheim GmbH, Eli Lilly and Company. Speaker's Bureau; Self; Medtronic, Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novo Nordisk Inc., Roche Diabetes Care Health and Digital Solutions, Sanofi-Aventis, Takeda Development Centre Europe Ltd. F. Giorgino: Consultant; Self; Abbott, AstraZeneca, Boehringer Ingelheim GmbH. Research Support; Self; Eli Lilly and Company, Johnson & Johnson Services, Inc.. Consultant; Self; MedImmune, Merck Sharp & Dohme Corp., Roche Diabetes Care Health and Digital Solutions, Sanofi. Research Support; Self; Takeda Development Centre Europe Ltd..