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

Nicola Marrano,Francesco Giorgino,Rosaria Spagnuolo,Annalisa Natalicchio,Giuseppina Biondi,Sebastio Perrini,Angelo Cignarelli,Luigi Laviola,Leonardo Vincenti

doi:10.3390/plants10020286

Abstract

Extra virgin olive oil (EVOO) is a major component of the Mediterranean diet and is appreciated worldwide because of its nutritional benefits in metabolic diseases, including type 2 diabetes (T2D). EVOO contains significant amounts of secondary metabolites, such as phenolic compounds (PCs), that may positively influence the metabolic status. In this study, we investigated for the first time the effects of several PCs on beta-cell function and survival. To this aim, INS-1E cells were exposed to 10 μM of the main EVOO PCs for up to 24 h. Under these conditions, survival, insulin biosynthesis, glucose-stimulated insulin secretion (GSIS), and intracellular signaling activation (protein kinase B (AKT) and cAMP response element-binding protein (CREB)) were evaluated. Hydroxytyrosol, tyrosol, and apigenin augmented beta-cell proliferation and insulin biosynthesis, and apigenin and luteolin enhanced the GSIS. Conversely, vanillic acid and vanillin were pro-apoptotic for beta-cells, even if they increased the GSIS. In addition, oleuropein, p-coumaric, ferulic and sinapic acids significantly worsened the GSIS. Finally, a mixture of hydroxytyrosol, tyrosol, and apigenin promoted the GSIS in human pancreatic islets. Apigenin was the most effective compound and was also able to activate beneficial intracellular signaling. In conclusion, this study shows that hydroxytyrosol, tyrosol, and apigenin foster beta-cells’ health, suggesting that EVOO or supplements enriched with these compounds may improve insulin secretion and promote glycemic control in T2D patients.

Highlights

Diabetes mellitus describes a group of metabolic disorders characterized by chronically elevated glycemia
To evaluate the impact of phenolic compounds (PCs) on beta-cell survival, INS-1E cells were treated for 24 h with 10 μM of the most important PCs identified in Extra virgin olive oil (EVOO)
Tyrosol, and apigenin foster beta-cell health by promoting proliferation and improving insulin biosynthesis, as well as by enhancing the glucose-stimulated insulin secretion (GSIS), without affecting apoptosis levels (Figure 1B)

Summary

Introduction

Diabetes mellitus describes a group of metabolic disorders characterized by chronically elevated glycemia. It represents one of the fastest-growing health challenges of the 21st century, with the number of adults living with diabetes having more than tripled over the past 20 years [1]. The loss of beta-cell functional mass is a necessary and early condition in the development of T2D [2]. Beta-cell restoration or regeneration should be strongly considered for the treatment, and possible cure, of T2D. A truly efficient antidiabetes therapeutic strategy capable of preventing the onset and progression of T2D should possess the capacity to stop beta-cell loss and/or promote the restoration of the fully functional beta-cell mass [2]

Methods

Results

Conclusion