Department of R & D, Sunchang Research Center for Fermentation Microbes, Sunchang-Gun, Sunchang-yup 56048, Korea.
Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Korea.
Nutrients. 2018 Oct 29;10(11):1588. doi: 10.3390/nu10111588.
We hypothesized that soybeans fermented with spp. for 48 h (chungkookjang) would be rich in poly-γ-glutamate (γ-PGA) and would have greater efficacy for improving insulin sensitivity and insulin secretion in 3T3-L1 adipocytes, min6 cells, and PC12 neuronal cells. We screened 20 different strains of and spp. for γ-polyglutamate (PGA) production and their anti-diabetic and anti-dementia activities in cell-based studies. Chungkookjang made with two spp. (BA730 and BA731) were selected to increase the isoflavonoid and γ-PGA. Insulin-stimulated glucose uptake was higher in 3T3-L1 adipocytes given both chungkookjang extracts than in the cells given vehicle (control). The ethanol extract of BA731 (BA731-E) increased the uptake the most. Triglyceride accumulation decreased in BA731-E and BA731-W and the accumulation increased in BA730-W and BA730-E. The mRNA expression of fatty acid synthetase and acetyl CoA carboxylase was much lower in BA731-E and BA731-W and it was higher in BA730-W than the control. BA730-E and BA730-W also increased peroxisome proliferator-activated receptor (PPAR)-γ activity. Glucose-stimulated insulin secretion increased with the high dosage of BA730-W and BA730-E in insulinoma cells, compared to the control. Insulin contents and cell survival in high glucose media were higher in cells with both BA731-E and BA730-E. Triglyceride deposition and TNF-α mRNA expression were lower in BA731 than the control. The high-dosage treatment of BA730-E and BA731-E increased differentiated neuronal cell survival after treating amyloid-β(25-35) compared to the control. Brain-derived neurotrophic factor and ciliary neurotrophic factor, indices of neuronal cell proliferation, were higher in BA730 and BA731 than in the control. Tau expression was also reduced in BA731 more than the control and it was a similar level of the normal-control. In conclusion, BA730 increased PPAR-γ activity and BA731 enhanced insulin sensitivity in the brain and periphery. BA730 and BA731 prevented and alleviated the symptoms of type 2 diabetes and Alzheimer's disease with different pathways.
我们假设，经过 48 小时发酵的大豆（chungkookjang）富含多聚γ-谷氨酸（γ-PGA），并能有效改善 3T3-L1 脂肪细胞、MIN6 细胞和 PC12 神经细胞的胰岛素敏感性和胰岛素分泌功能。我们从 20 株不同的 和 中筛选出γ-多聚谷氨酸（PGA）产生菌株，并在细胞水平研究它们的抗糖尿病和抗痴呆活性。我们选择两种 （BA730 和 BA731）来增加异黄酮和 γ-PGA，以制作 chungkookjang。与给予载体（对照）的细胞相比，给予两种 chungkookjang 提取物的 3T3-L1 脂肪细胞的胰岛素刺激葡萄糖摄取量更高。BA731 的乙醇提取物（BA731-E）增加了最多的摄取量。BA731-E 和 BA731-W 中甘油三酸酯的积累减少，而 BA730-W 和 BA730-E 中的积累增加。BA731-E 和 BA731-W 中的脂肪酸合成酶和乙酰辅酶 A 羧化酶的 mRNA 表达明显低于对照，而 BA730-W 高于对照。BA730-E 和 BA730-W 还增加了过氧化物酶体增殖物激活受体（PPAR）-γ 的活性。与对照相比，在胰岛素瘤细胞中，高剂量的 BA730-W 和 BA730-E 增加了葡萄糖刺激的胰岛素分泌。在高葡萄糖培养基中，BA731-E 和 BA730-E 处理后的胰岛素含量和细胞存活率均高于对照。BA731 中的甘油三酯沉积和 TNF-α mRNA 表达低于对照。与对照相比，高剂量的 BA730-E 和 BA731-E 处理后，淀粉样β（25-35）诱导的分化神经元细胞存活率增加。BA730 和 BA731 中的脑源性神经营养因子和睫状神经营养因子，神经元细胞增殖的指标，均高于对照。BA731 中的 Tau 表达也低于对照，且与正常对照水平相当。总之，BA730 增加了 PPAR-γ 活性，BA731 增强了大脑和外周组织的胰岛素敏感性。BA730 和 BA731 通过不同途径预防和缓解 2 型糖尿病和阿尔茨海默病的症状。
