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

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.

Olive Oil Lipophenols Induce Insulin Secretion in 832/13 β-Cell Models

“…Our results demonstrate that while Hty positively affected the hormone glucose stimulated secretion, Ty did not induce any change in insulin release in the culture medium. This finding is in agreement with recent observations, indicating a role for Ty in beta cell survival and in insulin biosynthesis, rather than on the GSIS [ 26 ]. Of note, the exposure of INS-1 832/13 β-cells to DC260126 did not influence the enabler effect of Hty on GSIS, indicating that the insulin secretagogue activity of this compound is not mediated by FFAR1 and in this respect, inhibition of K/ATP channels and the subsequent opening of the voltage-dependent calcium channel by Hty has been proposed [ 45 ].…”

“…The amount of HtyOle in EVOOs has been previously quantified as 4.9 mg kg −1 of oil [ 32 ], while TyOle was found in the range 0.17–1.18 mg kg −1 of oil, depending on the cultivar of the plant from which the olive oil originates [ 33 ]. The anti-diabetic effects of olive oil have been associated with the high content of OA [ 7 , 8 , 9 , 10 ], as well as with its phenolic fraction [ 25 , 26 , 27 , 43 ]. On the basis of the effects observed in this study, HtyOle and TyOle may be partly responsible for the anti-diabetic effects associated with olive oil consumption.…”

“…Furthermore, Hauke et al measured the content of endogenous fatty acids released from membrane phospholipids in which OA was present at ng amounts [ 53 ]. On the other hand, both Hty and Ty have been shown to preserve β-cell function and survival through the activation of anti-inflammatory and antioxidant pathways [ 26 ]. Our future research directions will be devoted to the preparation of structurally related and modified lipophenols, in which the phenolic OH groups could be replaced by one or two methoxy groups.…”

“…On the other hand, phenolic compounds are known to contribute to EVOO health benefits, even if they represent a minor fraction in the composition of olive oil [ 25 ]. In this context, hydroxytyrosol (Hty) and tyrosol (Ty) have been shown to preserve β-cell function and survival, and to exert anti-diabetic effect in animal models of T2DM [ 26 , 27 ]. However, the polar nature of Hty and Ty and their unfavorable pharmacokinetic profiles has hampered the use of these compounds in humans.…”

Olive Polyphenols: Antioxidant and Anti-Inflammatory Properties

“…The molecular determinants of the protection by olive polyphenols against several aging-associated and chronic degenerative conditions, including T2DM [21][22][23] and nonalcoholic fatty liver disease [24][25][26][27][28], have been extensively investigated in the last 20 years. OLE, HT and other olive polyphenols protect cells against oxidative damage resulting from redox dyshomeostasis [29,30] and an excessive inflammatory response [31], among the main determinants of age-related pathologies such as cancer, T2DM, MetS, osteoporosis and neurological diseases [27,32].…”