Oleuropein, a natural product derived from olive leaves, has reported anti-diabetic functions. However, detailed molecular mechanisms for how it affects β-cell functions remain poorly understood. Here, we present evidence that oleuropein promotes glucose-stimulated insulin secretion (GSIS) in β-cells. The effect is dose-dependent and stimulates the ERK/MAPK signaling pathway. We further demonstrated that oleuropein inhibits the cytotoxicity induced by amylin amyloids, a hallmark feature of type 2 diabetes. We demonstrated that these dual functions are structure-specific: we identified the 3-hydroxytyrosol moiety of oleuropein as the main functional entity responsible for amyloid inhibition, but the novel GSIS function requires the entire structure scaffold of the molecule.

中文翻译：

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橄榄成分橄榄苦苷可促进β细胞胰岛素分泌并保护β细胞免受淀粉样淀粉样蛋白诱导的细胞毒性作用

橄榄苦苷，一种来自橄榄叶的天然产物，据报道具有抗糖尿病作用。然而，关于它如何影响β细胞功能的详细分子机制仍然知之甚少。在这里，我们提供证据表明橄榄苦苷可促进β细胞中葡萄糖刺激的胰岛素分泌（GSIS）。该作用是剂量依赖性的，并且刺激ERK / MAPK信号传导途径。我们进一步证明，橄榄苦苷可以抑制胰岛淀粉样淀粉样蛋白（2型糖尿病的标志性特征）诱导的细胞毒性。我们证明了这些双重功能是特定于结构的：我们确定了橄榄苦苷的3-羟基酪醇部分是负责淀粉样蛋白抑制的主要功能实体，但新的GSIS功能需要分子的整个结构支架。