A popular fermented soybean food of Northeast India exerted promising antihyperglycemic potential via stimulating PI3K/AKT/AMPK/GLUT4 signaling pathways and regulating muscle glucose metabolism in type 2 diabetes
Dibyendu Das
Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for more papers by this authorSanjib Sarkar
Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for more papers by this authorAnjum Dihingia
Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Search for more papers by this authorNazim Uddin Afzal
Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for more papers by this authorSawlang Borsingh Wann
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Search for more papers by this authorCorresponding Author
Jatin Kalita
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Correspondence
Jatin Kalita and Prasenjit Manna, Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat-785006, Assam, India.
Email: [email protected] (J. K.) and [email protected] (P. M.)
Saikat Dewanjee, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Saikat Dewanjee
Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
Correspondence
Jatin Kalita and Prasenjit Manna, Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat-785006, Assam, India.
Email: [email protected] (J. K.) and [email protected] (P. M.)
Saikat Dewanjee, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Prasenjit Manna
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Correspondence
Jatin Kalita and Prasenjit Manna, Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat-785006, Assam, India.
Email: [email protected] (J. K.) and [email protected] (P. M.)
Saikat Dewanjee, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Email: [email protected]
Search for more papers by this authorDibyendu Das
Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for more papers by this authorSanjib Sarkar
Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for more papers by this authorAnjum Dihingia
Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Search for more papers by this authorNazim Uddin Afzal
Biological Sciences and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Search for more papers by this authorSawlang Borsingh Wann
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Search for more papers by this authorCorresponding Author
Jatin Kalita
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Correspondence
Jatin Kalita and Prasenjit Manna, Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat-785006, Assam, India.
Email: [email protected] (J. K.) and [email protected] (P. M.)
Saikat Dewanjee, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Saikat Dewanjee
Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India
Correspondence
Jatin Kalita and Prasenjit Manna, Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat-785006, Assam, India.
Email: [email protected] (J. K.) and [email protected] (P. M.)
Saikat Dewanjee, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Prasenjit Manna
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India
Correspondence
Jatin Kalita and Prasenjit Manna, Center for Infectious Diseases, CSIR-North East Institute of Science and Technology, Jorhat-785006, Assam, India.
Email: [email protected] (J. K.) and [email protected] (P. M.)
Saikat Dewanjee, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Email: [email protected]
Search for more papers by this authorAbstract
This study examined the antidiabetic efficacy of popular fermented soybean foods (FSF) of Northeast (NE) India. Results showed that among different FSF, aqueous extract of Hawaijar (AEH), a traditional FSF of Manipur, NE India, significantly augmented glucose utilization in cultured myotubes treated with high glucose (HG, 25 mM). Furthermore, AEH also upregulated glucose uptake, glucose-6-phosphate level, and phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 protein expression in HG-treated myotubes. In vivo studies demonstrated that AEH supplementation (50, 100, or 200 mg/kg body weight/day, oral gavaging, 16 weeks) reduced body weight, fasting blood glucose, glycated hemoglobin, insulin resistance, and glucose intolerance in rats fed with high-fat diet (HFD). AEH supplementation stimulated phopho-PI3K/phospho-AKT/phospho-AMPK/GLUT4 signaling cascades involved in glucose metabolism of muscle tissues in diabetic rats. Chemical profiling of AEH (SDS-PAGE, immunoblotting, and HRMS) suggests the possible role of bioactive proteins/peptides and isoflavones underlying the antihyperglycemic potential AEH. Results from this study will be helpful for developing food-based prophylactics/therapeutics in managing hyperglycemia.
Practical applications
Fermented soybean foods are gaining acceptance due to multiple health benefits. This study for the first time reports the antidiabetic potential of Hawaijar, an indigenous fermented soybean food of North-East India. Higher abundance of bioactive compounds (isoflavones and proteins/peptides) in Hawaijar may be responsible for the alleviation of impaired glucose metabolism associated with diabetes. The findings may be helpful for the development of a novel therapeutic to achieve better control of hyperglycemia and improve the lives of the patient population with diabetes.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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REFERENCES
- Alfarouk, K. O., Verduzco, D., Rauch, C., Muddathir, A. K., Bashir, A. H., Elhassan, G. O., Ibrahim, M. E., Orozco, J. D. P., Cardone, R. A., Reshkin, S. J., & Harguindey, S. (2015). Erratum: Glycolysis, tumor metabolism, cancer growth and dissemination. A new pH-based etiopathogenic perspective and therapeutic approach to an old cancer question. Oncoscience, 2(4), 317. https://doi.org/10.18632/oncoscience.158
- Chen, Y.-J., Baskaran, R., Chang, C. F., Mohammedsaleh, Z. M., & Lin, W.-T. (2022). Decapeptide from potato hydrolysate induces myogenic differentiation and ameliorates high glucose-associated modulations in protein synthesis and mitochondrial biogenesis in C2C12 cells. Biomolecules, 12(4), 565.
- Cheong, S. H., Furuhashi, K., Ito, K., Nagaoka, M., Yonezawa, T., Miura, Y., & Yagasaki, K. (2014). Daidzein promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and improves glucose homeostasis in Type 2 diabetic model mice. The Journal of Nutritional Biochemistry, 25(2), 136–143. https://doi.org/10.1016/j.jnutbio.2013.09.012
- Cho, D., Mier, J. W., & Atkins, M. B. (2009). PI3K/Akt/mTOR pathway: A growth and proliferation pathway. In R. M. Bukowski, R. A. Figlin, & R. J. Motzer (Eds.), Renal cell carcinoma: Molecular targets and clinical applications (pp. 267–285). Humana Press.
10.1007/978-1-59745-332-5_15 Google Scholar
- Chove, B. E., Grandison, A. S., & Lewis, M. J. (2001). Emulsifying properties of soy protein isolate fractions obtained by isoelectric precipitation. Journal of the Science of Food and Agriculture, 81(8), 759–763. https://doi.org/10.1002/jsfa.877
- Das, D., Sarkar, S., Bordoloi, J., Wann, S. B., Kalita, J., & Manna, P. (2018). Daidzein, its effects on impaired glucose and lipid metabolism and vascular inflammation associated with type 2 diabetes. BioFactors, 44(5), 407–417. https://doi.org/10.1002/biof.1439
- Deka, B., Barge, S. R., Bharadwaj, S., Kashyap, B., Manna, P., Borah, J. C., & Talukdar, N. C. (2021). Beneficial effect of the methanolic leaf extract of Allium hookeri on stimulating glutathione biosynthesis and preventing impaired glucose metabolism in type 2 diabetes. Archives of Biochemistry and Biophysics, 708, 108961. https://doi.org/10.1016/j.abb.2021.108961
- Dihingia, A., Ozah, D., Baruah, P. K., Kalita, J., & Manna, P. (2018). Prophylactic role of vitamin K supplementation on vascular inflammation in type 2 diabetes by regulating the NF-kappaB/Nrf2 pathway via activating Gla proteins. Food & Function, 9(1), 450–462. https://doi.org/10.1039/c7fo01491k
- Dihingia, A., Ozah, D., Borah, T., Kalita, J., & Manna, P. (2020). Gamma-glutamyl-carboxylated Gas6 mediates positive role of vitamin K on lowering hyperglycemia in type 2 diabetes. Annals of the New York Academy of Sciences, 1462(1), 104–117. https://doi.org/10.1111/nyas.14238
- Evans, P. L., McMillin, S. L., Weyrauch, L. A., & Witczak, C. A. (2019). Regulation of skeletal muscle glucose transport and glucose metabolism by exercise training. Nutrients, 11(10), 2432. https://doi.org/10.3390/nu11102432
- Gilbert, E. R., & Liu, D. (2013). Anti-diabetic functions of soy isoflavone genistein: Mechanisms underlying its effects on pancreatic β-cell function. Food & Function, 4(2), 200–212. https://doi.org/10.1039/c2fo30199g
- Grant, G. (1989). Anti-nutritional effects of soybean: A review. Progress in Food & Nutrition Science, 13(3–4), 317–348.
- Huang, X., Liu, G., Guo, J., & Su, Z. (2018). The PI3K/AKT pathway in obesity and type 2 diabetes. International Journal of Biological Sciences, 14(11), 1483–1496. https://doi.org/10.7150/ijbs.27173
- Ismael, M. A., Talbot, S., Carbonneau, C. L., Beauséjour, C. M., & Couture, R. (2008). Blockade of sensory abnormalities and kinin B(1) receptor expression by N-acetyl-L-cysteine and ramipril in a rat model of insulin resistance. European Journal of Pharmacology, 589(1–3), 66–72. https://doi.org/10.1016/j.ejphar.2008.05.006
- Jiang, P., Ren, L., Zhi, L., Yu, Z., Lv, F., Xu, F., Peng, W., Bai, X., Cheng, K., Quan, L., Zhang, X., Wang, X., Zhang, Y., Yang, D., Hu, X., & Xiao, R. P. (2021). Negative regulation of AMPK signaling by high glucose via E3 ubiquitin ligase MG53. Molecular Cell, 81(3), 629–637.e625. https://doi.org/10.1016/j.molcel.2020.12.008
- Kashyap, B., Barge, S. R., Bharadwaj, S., Deka, B., Rahman, S., Ghosh, A., Manna, P., Dutta, P. P., Sheikh, Y., Kandimalla, R., KumarSamanta, S., Boruwa, J., Saikia, S., Swargiary, D., Kamboj, P., Tuli, D., Pal, U., Borah, J. C., Banerjee, S. K., & Talukdar, N. C. (2021). Evaluation of therapeutic effect of Premna herbacea in diabetic rat and isoverbascoside against insulin resistance in L6 muscle cells through bioenergetics and stimulation of JNK and AKT/mTOR signaling cascade. Phytomedicine, 93, 153761. https://doi.org/10.1016/j.phymed.2021.153761
- Keishing, S., Banu, T., & Umadevi, M. (2015). Effect of fermentation on the nutrient content, antioxidant and antidiabetic activities of Hawaijar, an indigenous fermented soya of Manipur, India. Journal of Human Nutrition & Food Science, 3(3), 1066–1070.
- Kim, S. Y., Park, P. S. W., & Rhee, K. C. (1990). Functional properties of proteolytic enzyme modified soy protein isolate. Journal of Agricultural and Food Chemistry, 38, 651–656.
- Kjøbsted, R., Hingst, J. R., Fentz, J., Foretz, M., Sanz, M. N., Pehmøller, C., Shum, M., Marette, A., Mounier, R., Treebak, J. T., Wojtaszewski, J. F. P., Violletb, B., & Lantier, L. (2018). AMPK in skeletal muscle function and metabolism. The FASEB Journal, 32(4), 1741–1777. https://doi.org/10.1096/fj.201700442R
- Kwon, D., Daily Iii, J., Kim, H., & Park, S. (2010). Antidiabetic effects of fermented soybean products on type 2 diabetes. Nutrition Research (New York, N.Y.), 30, 1–13. https://doi.org/10.1016/j.nutres.2009.11.004
- Lammi, C., Zanoni, C., & Arnoldi, A. (2015). Three peptides from soy glycinin modulate glucose metabolism in human hepatic HepG2 cells. International Journal of Molecular Sciences, 16(11), 27362–27370. https://doi.org/10.3390/ijms161126029
- Lammi, C., Zanoni, C., Arnoldi, A., & Vistoli, G. (2015). Two peptides from soy β-conglycinin induce a hypocholesterolemic effect in HepG2 cells by a statin-like mechanism: Comparative in vitro and in silico modeling studies. Journal of Agricultural and Food Chemistry, 63(36), 7945–7951. https://doi.org/10.1021/acs.jafc.5b03497
- Lee, M. S., Kim, C. H., Hoang, D. M., Kim, B. Y., Sohn, C. B., Kim, M. R., & Ahn, J. S. (2009). Genistein-derivatives from Tetracera scandens stimulate glucose-uptake in L6 myotubes. Biological & Pharmaceutical Bulletin, 32(3), 504–508. https://doi.org/10.1248/bpb.32.504
- Luo, W., Ai, L., Wang, B. F., & Zhou, Y. (2019). High glucose inhibits myogenesis and induces insulin resistance by down-regulating AKT signaling. Biomedicine & Pharmacotherapy, 120, 109498. https://doi.org/10.1016/j.biopha.2019.109498
- Manna, P., & Jain, S. K. (2012). Vitamin D up-regulates glucose transporter 4 (GLUT4) translocation and glucose utilization mediated by cystathionine-gamma-lyase (CSE) activation and H2S formation in 3T3L1 adipocytes. The Journal of Biological Chemistry, 287(50), 42324–42332. https://doi.org/10.1074/jbc.M112.407833
- Manna, P., & Jain, S. K. (2013). L-cysteine and hydrogen sulfide increase PIP3 and AMPK/PPARγ expression and decrease ROS and vascular inflammation markers in high glucose treated human U937 monocytes. Journal of Cellular Biochemistry, 114(10), 2334–2345. https://doi.org/10.1002/jcb.24578
- Martinez-Villaluenga, C., Dia, V. P., Berhow, M., Bringe, N. A., & Gonzalez de Mejia, E. (2009). Protein hydrolysates from beta-conglycinin enriched soybean genotypes inhibit lipid accumulation and inflammation in vitro. Molecular Nutrition & Food Research, 53(8), 1007–1018. https://doi.org/10.1002/mnfr.200800473
- Merz, K. E., & Thurmond, D. C. (2020). Role of skeletal muscle in insulin resistance and glucose uptake. Comprehensive Physiology, 10(3), 785–809. https://doi.org/10.1002/cphy.c190029
- Ramachandran, V., & Saravanan, R. (2015). Glucose uptake through translocation and activation of GLUT4 in PI3K/Akt signaling pathway by asiatic acid in diabetic rats. Human & Experimental Toxicology, 34(9), 884–893. https://doi.org/10.1177/0960327114561663
- Reddy, N. R., & Pierson, M. D. (1994). Reduction in antinutritional and toxic components in plant foods by fermentation. The term ‘plant foods’ is used in the context of food derived from plant sources. Food Research International, 27(3), 281–290. https://doi.org/10.1016/0963-9969(94)90096-5
- Sami, W., Ansari, T., Butt, N. S., & Hamid, M. R. A. (2017). Effect of diet on type 2 diabetes mellitus: A review. International Journal of Health Sciences (Qassim), 11(2), 65–71.
- Sanjukta, S., & Rai, A. K. (2016). Production of bioactive peptides during soybean fermentation and their potential health benefits. Trends in Food Science & Technology, 50, 1–10. https://doi.org/10.1016/j.tifs.2016.01.010
- Shrestha, P., & Ghimire, L. (2012). A review about the effect of life style modification on diabetes and quality of life. Global Journal of Health Science, 4(6), 185–190. https://doi.org/10.5539/gjhs.v4n6p185
- Song, Y. S., Frias, J., Martinez-Villaluenga, C., Vidal-Valdeverde, C., & de Mejia, E. G. (2008). Immunoreactivity reduction of soybean meal by fermentation, effect on amino acid composition and antigenicity of commercial soy products. Food Chemistry, 108(2), 571–581. https://doi.org/10.1016/j.foodchem.2007.11.013
- Sun, H., Liu, X., Wang, Y.-Z., Liu, J.-X., & Feng, J. (2013). Soybean glycinin- and β-conglycinin-induced intestinal immune responses in a murine model of allergy. Food and Agricultural Immunology, 24(3), 357–369. https://doi.org/10.1080/09540105.2012.704507
- Tamang, J. (2015). Naturally fermented ethnic soybean foods of India. Journal of Ethnic Foods, 55, 8–17. https://doi.org/10.1016/j.jef.2015.02.003
10.1016/j.jef.2015.02.003 Google Scholar
- Tang, G., Du, Y., Guan, H., Jia, J., Zhu, N., Shi, Y., Rong, S., & Yuan, W. (2022). Butyrate ameliorates skeletal muscle atrophy in diabetic nephropathy by enhancing gut barrier function and FFA2-mediated PI3K/Akt/mTOR signals. British Journal of Pharmacology, 179(1), 159–178. https://doi.org/10.1111/bph.15693
- Yamanishi, R., Huang, T., Tsuji, H., Bando, N., & Ogawa, T. (1995). Reduction of the soybean allergenicity by the fermentation with Bacillus natto. Food Science and Technology International, Tokyo, 1(1), 14–17. https://doi.org/10.3136/fsti9596t9798.1.14
10.3136/fsti9596t9798.1.14 Google Scholar
- Yap, A., Nishiumi, S., Yoshida, K., & Ashida, H. (2007). Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives. Cytotechnology, 55(2–3), 103–108. https://doi.org/10.1007/s10616-007-9107-y
- Yu, S., Liu, L., Bu, T., Zheng, J., Wang, W., Wu, J., & Liu, D. (2022). Purification and characterization of hypoglycemic peptides from traditional Chinese soy-fermented douchi. Food & Function, 13(6), 3343–3352. https://doi.org/10.1039/D1FO03941E
