Blueberry fruit exhibits strong antioxidant activity owing to the presence of anthocyanin. As blueberry-leaf extract (BLE) contains chlorogenic acid and flavonol glycosides, we hypothesized that phenolic-enriched BLE would improve glucose homeostasis and insulin sensitivity. In this study, we examined whether BLE administration decreases the glucose levels and enhances the pancreatic function in mice with high-fat diet (HFD)-induced obesity and diabetes. C57BL/6J mice were divided into the following four groups: control diet (CD), HFD (60 kcal% fat diet), BLE (HFD with 1% BLE wt/wt diet), and yerba mate extract (YME; HFD with 0.5% YME wt/wt diet). Dietary BLE and YME reduced glucose tolerance, body weight, and plasma glucose, glycated hemoglobin, insulin, homeostasis model assessment of insulin resistance, triglyceride (TG), and non-esterified fatty acid levels. Compared with those of the HFD group, BLE was found to significantly reduce the pancreatic islet size and insulin content. Moreover, it increased the mRNA levels of pancreatic β-cell proliferation-related genes, Ngn3, MafA, Pax4, Ins1, and Ins2, and pancreatic insulin signaling-related genes, IRS-1, IRS-2, PIK3ca, PDK1, PKCε, and GLUT-2, and decreased the transcriptional expression of the β-cell apoptosis-related gene, FoxO1. Both BLE and YME improved insulin sensitivity by inhibiting TG synthesis and enhancing lipid utilization in the liver and white adipose tissue (WAT). In pancreatic MIN6 β-cells, BLE and its main component (chlorogenic acid) increased β-cell proliferation and promoted insulin signaling. Overall, BLE enriched with phenolic compounds has the capacity to prevent HFD-induced glucose tolerance and hyperglycemia by improving the pancreatic β-cell function.

中文翻译：

---

富含酚类的蓝莓叶提取物减弱高脂饮食诱导的糖尿病小鼠的葡萄糖稳态、胰腺 β 细胞功能和胰岛素敏感性

由于花青素的存在，蓝莓果实具有很强的抗氧化活性。由于蓝莓叶提取物 (BLE) 含有绿原酸和黄酮醇糖苷，我们假设富含酚类的 BLE 会改善葡萄糖稳态和胰岛素敏感性。在这项研究中，我们检查了 BLE 给药是否会降低高脂饮食 (HFD) 诱导的肥胖和糖尿病小鼠的葡萄糖水平并增强其胰腺功能。C57BL/6J 小鼠分为以下四组：对照饮食 (CD)、HFD（60 kcal% 脂肪饮食）、BLE（HFD 与 1% BLE wt/wt 饮食）和马黛茶提取物（YME；HFD 与 0.5 % YME wt/wt 饮食）。膳食 BLE 和 YME 降低葡萄糖耐量、体重和血浆葡萄糖、糖化血红蛋白、胰岛素、胰岛素抵抗的稳态模型评估、甘油三酯 (TG)、和非酯化脂肪酸水平。与HFD组相比，发现BLE显着降低胰岛大小和胰岛素含量。此外，它增加了胰腺 β 细胞增殖相关基因 Ngn3、MafA、Pax4、Ins1 和 Ins2 以及胰腺胰岛素信号相关基因 IRS-1、IRS-2、PIK3ca、PDK1、PKCε、和 GLUT-2，并降低 β 细胞凋亡相关基因 FoxO1 的转录表达。BLE 和 YME 均通过抑制 TG 合成和增强肝脏和白色脂肪组织 (WAT) 中的脂质利用来改善胰岛素敏感性。在胰腺 MIN6 β 细胞中，BLE 及其主要成分（绿原酸）增加了 β 细胞增殖并促进了胰岛素信号传导。全面的，