Chungkookjang with High Contents of Poly-γ-Glutamic Acid Improves Insulin Sensitizing Activity in Adipocytes and Neuronal Cells

Abstract

We hypothesized that soybeans fermented with Bacillus 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 B. subtillus and B. amyloliquefaciens spp. for γ-polyglutamate (PGA) production and their anti-diabetic and anti-dementia activities in cell-based studies. Chungkookjang made with two B. amyloliquefaciens 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.

Dietary Protein Consumption and the Risk of Type 2 Diabetes: ADose-Response Meta-Analysis of Prospective Studies

“…Several beneficial components of soy products may contribute to the hypoglycemic effect, including isoflavones and soy protein [97]. A cell-based study suggested that soy protein and isoflavones are beneficial for reducing the risk of onset and development of insulin resistance and T2D and a review also showed that fermented soy products may attenuate the progression of T2D by improving insulin resistance and insulin secretion [98,99]. A pooled analysis reported that isoflavones can improve hyperglycemia, glucose tolerance, and circulating insulin concentration, and can also stimulate phosphorylated AMP-activated protein kinase and acetyl-CoA carboxylase to increase glucose uptake and fatty acid oxidation [60].…”

γ-PGA-Rich Chungkookjang, Short-Term Fermented Soybeans: Prevents Memory Impairment by Modulating Brain Insulin Sensitivity, Neuro-Inflammation, and the Gut–Microbiome–Brain Axis

“…The different types of chungkookjang demonstrate unique functionalities. Chungkookjang containing high γ-PGA has better efficacy for improving glucose metabolism and neuronal cell survival [ 5 ]. Fermenting with specific Bacillus species to change bioactive components, including the generation of higher γ-PGA, may enhance the functionality of chungkookjang [ 7 ].…”

“…Chungkookjang traditionally made in Sunchang, Chonbuk-Do, Korea, has been reported to promote insulin sensitivity and subsequently to protect against type 2 diabetes and Alzheimer’s disease progression [ 5 , 14 , 15 ]. Subjects who consumed traditionally made chungkookjang (26 g/day) exhibited a decrease in apolipoprotein B compared to those who consumed a placebo ( p < 0.05) in a 12-week randomized clinical trial [ 16 ].…”

“…The fermented soybeans have been reported to have more beneficial functions than unfermented soybeans for type 2 diabetes when they are optimally made [ 4 , 5 , 6 , 7 , 8 ]. Soybeans contain proteins, isoflavone glycosides, soluble dietary fiber, and fats, and they are beneficial for glucose and lipid metabolism [ 9 , 10 , 11 ].…”

Effects of &lt;i&gt;γ&lt;/i&gt;-Polyglutamic Acid on Blood Glucose and Caecal Short Chain Fatty Acids in Adult Male Mice

“…It has been reported that soybeans fermented by Bacillus spp. possess high γ-PGA content that can improve insulin-sensitizing activity in adipocytes and neuronal cells [8]. From available reports, γ-PGA appears to be effective for improving lipid metabolism and glucose metabolism.…”