Revealing the Hypoglycemic Effects and Mechanism of GABA-Rich Germinated Adzuki Beans on T2DM Mice by Untargeted Serum Metabolomics

Abstract

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic diseases, and exploring strategies to prevent and treat diabetes has become extremely important. In recent decades the search for new therapeutic strategies for T2DM involving dietary interventions has attracted public attention. We established a diabetic mouse model by feeding mice a high-fat diet combined with injection of low-dose streptozotocin, intending to elucidate the effects and possible mechanisms of different dosages of γ-aminobutyric acid (GABA)-rich germinated adzuki beans on the treatment of diabetes in mice. The mice were treated for 6 weeks either with increasing doses of GABA-enriched germinated adzuki beans, with non-germinated adzuki beans, with GABA, or with the positive control drug metformin. Then, the blood glucose levels and blood lipid biochemical indicators of all the mice were measured. At the same time, serum differential metabolite interactions were explored by UPLC-Q/TOF-MS-based serum metabolomic analysis. The results showed that body weight and fasting blood glucose levels were significantly reduced (P < 0.05). We also report improved levels of total cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, urea, and serum creatinine. We observed a significant improvement in the homeostasis model assessment of the beta cell function and insulin resistance (HOMA-β and HOMA-IR) scores (P < 0.05) in the group of mice treated with the highest dose of GABA-enriched germinated adzuki beans. In addition, the metabolic profiles of the serum were analyzed, and 31 differential metabolites including amino acids and lipids were obtained. According to the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, this was found to be correlated with nine significantly enriched metabolic pathways involving the up-regulation of levels of L-serine, SM (d18:1/22:1(13Z)), L-histidine, creatine, and 3-indoleacetic acid. Our data suggest that the hypoglycemic effect of GABA-enriched germinated adzuki beans on diabetic mice may be related to improving tryptophan metabolism, glycerol phospholipid metabolism, sphingosline metabolism, and the glycine, serine, and threonine metabolic pathways. This study provides a reference for the application of GABA-enriched germinated foods in type 2 diabetes and could provide a cue for searching biomarkers to be adopted for T2DM diagnosis.

Metformin Mitigates Memory Impairment of Diabetic Mice through Modulation of Plasma Pro-inflammatory Cytokines and Aβ1-42 Levels

“…We showed that metformin treatment rescued cognitive deficits in T2DM mice induced by HFD feeding combined with STZ injection. This finding was consistent with previous studies revealing the protective effects of metformin against HFD/STZ-induced cognitive impairments in the animal model of T2DM (Salman et al, 2013;Jiang et al, 2021). Although the effect of metformin treatment per se on cognitive function in non-diabetic control animals was not investigated in the present study, Oliveira and colleagues reported that oral treatment with metformin at the dose of 200 mg/kg for 21 days had no effect on cognition (Oliveira et al, 2016).…”

Research Update on the Impact of Lactic Acid Bacteria on the Substance Metabolism, Flavor, and Quality Characteristics of Fermented Meat Products

“…Fadda et al [ 32 ] and Sanz et al [ 33 ] reported that L. plantarum ’s enzyme system can break down myogenic fibronectin and sarcoplasmic proteins into small active peptides and free the amino acids through the action of proteases. Free amino acids are mostly used as a source of flavor substances and can also produce various flavor components under the action of different enzymes; for example, valine has the aroma of malt, glycine and threonine are sources of sweet flavors; glutamic acid is a source of fresh and savory flavors, and aminobutyric acid produced by glutamic acid under the action of decarboxylase can also prevent diabetes [ 34 ]. The accumulation of various peptides and amino acids facilitates the enhancement of meat aroma and flavor.…”

The Potential of the Adzuki Bean (Vigna angularis) and Its Bioactive Compounds in Managing Type 2 Diabetes and Glucose Metabolism: A Narrative Review

“…Another way to process adzuki beans is germination, a food processing technique that alters the nutritional and functional properties of the seeds. An animal study conducted by both Jiang et al [ 46 ] and Zhang et al [ 47 ] used germination (31 °C for 48 h, humidity of 95 ± 3%, sprayed with 2 mmol/L monosodium glutamate once every hour) to increase the GABA content in the adzuki beans, and reported that germinated GABA (γ-aminobutyric acid)-rich adzuki beans had an anti-diabetic impact. Jiang et al [ 46 ] found that a high-fat diet significantly increased the serum glucose and HOMA-IR levels while significantly decreasing insulin and HOMA-β levels of the mice ( p < 0.05).…”

“…An animal study conducted by both Jiang et al [ 46 ] and Zhang et al [ 47 ] used germination (31 °C for 48 h, humidity of 95 ± 3%, sprayed with 2 mmol/L monosodium glutamate once every hour) to increase the GABA content in the adzuki beans, and reported that germinated GABA (γ-aminobutyric acid)-rich adzuki beans had an anti-diabetic impact. Jiang et al [ 46 ] found that a high-fat diet significantly increased the serum glucose and HOMA-IR levels while significantly decreasing insulin and HOMA-β levels of the mice ( p < 0.05). Providing the mice with 35 g adzuki bean/100 g diet for 5 weeks resulted in no statistically significant differences in serum glucose and insulin levels, while significantly lowering the HOMA-IR level of the mice.…”