Department of Nutrition, Dietetics and Food Science, Brigham Young University, Provo, UT.
Department of Food Science and Technology, Virginia Tech, Blacksburg, VA.
J Nutr Biochem. 2017 Nov;49:30-41. doi: 10.1016/j.jnutbio.2017.07.015. Epub 2017 Jul 27.
A hallmark of type 2 diabetes (T2D) is β-cell dysfunction and the eventual loss of functional β-cell mass. Therefore, mechanisms that improve or preserve β-cell function could be used to improve the quality of life of individuals with T2D. Studies have shown that monomeric, oligomeric and polymeric cocoa flavanols have different effects on obesity, insulin resistance and glucose tolerance. We hypothesized that these cocoa flavanols may have beneficial effects on β-cell function. INS-1 832/13-derived β-cells and primary rat islets cultured with a monomeric catechin-rich cocoa flavanol fraction demonstrated enhanced glucose-stimulated insulin secretion, while cells cultured with total cocoa extract and with oligomeric or polymeric procyanidin-rich fraction demonstrated no improvement. The increased glucose-stimulated insulin secretion in the presence of the monomeric catechin-rich fraction corresponded with enhanced mitochondrial respiration, suggesting improvements in β-cell fuel utilization. Mitochondrial complex III, IV and V components are up-regulated after culture with the monomer-rich fraction, corresponding with increased cellular ATP production. The monomer-rich fraction improved cellular redox state and increased glutathione concentration, which corresponds with nuclear factor, erythroid 2 like 2 (Nrf2) nuclear localization and expression of Nrf2 target genes including nuclear respiratory factor 1 (Nrf1) and GA binding protein transcription factor alpha subunit (GABPA), essential genes for increasing mitochondrial function. We propose a model by which monomeric cocoa catechins improve the cellular redox state, resulting in Nrf2 nuclear migration and up-regulation of genes critical for mitochondrial respiration, glucose-stimulated insulin secretion and ultimately improved β-cell function. These results suggest a mechanism by which monomeric cocoa catechins exert their effects as an effective complementary strategy to benefit T2D patients.
2 型糖尿病（T2D）的一个标志是β细胞功能障碍和功能性β细胞质量的最终丧失。因此，改善或维持β细胞功能的机制可用于提高 T2D 患者的生活质量。研究表明，单体、寡聚体和多聚体可可黄烷醇对肥胖、胰岛素抵抗和葡萄糖耐量有不同的影响。我们假设这些可可黄烷醇可能对β细胞功能有有益的影响。用单体儿茶素丰富的可可黄烷醇部分培养的 INS-1 832/13 衍生的β细胞和原代大鼠胰岛显示出增强的葡萄糖刺激的胰岛素分泌，而用总可可提取物和寡聚体或多聚体原花青素丰富的部分培养的细胞则没有改善。单体儿茶素丰富部分存在时增加的葡萄糖刺激的胰岛素分泌与增强的线粒体呼吸相对应，表明β细胞燃料利用的改善。培养后，单体丰富部分上调了线粒体复合物 III、IV 和 V 成分，对应于细胞 ATP 产量的增加。单体丰富部分改善了细胞氧化还原状态并增加了谷胱甘肽浓度，这与核因子、红细胞 2 样 2（Nrf2）核定位和 Nrf2 靶基因包括核呼吸因子 1（Nrf1）和 GA 结合蛋白转录因子α亚基（GABPA）的表达相对应，这些基因对于增加线粒体功能至关重要。我们提出了一个模型，即单体可可儿茶素通过改善细胞氧化还原状态，导致 Nrf2 核迁移和上调与线粒体呼吸、葡萄糖刺激的胰岛素分泌以及最终改善β细胞功能相关的关键基因。这些结果表明，单体可可儿茶素通过发挥作用的机制作为一种有效的补充策略，有益于 T2D 患者。
