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(1) A novel antidiabetic peptide (GPAGAP) was screened by Network pharmacology.
(2) GPAGAP is predicted to ameliorate type 2 diabetes through multiple pathways and multiple targets.
(3) GPAGAP can improve the glucose metabolism disorder of IR-HepG2 cells.
(4) GPAGAP can improve the lipid metabolism disorder of IR-HepG2 cells.
(5) GPAGAP can improve the oxidative stress level of IR-HepG2 cells.
In this study, a novel hypoglycemic peptide Gly-Pro-Ala-Gly-Ala-Pro (GPAGAP) was screened from skin collagen hydrolysates of Andrias davidianus by network pharmacology and bioinformatics, and its hypoglycemic mechanism was predicted. Meanwhile, the improvement of insulin resistance (IR) in HepG2 cells were detected. Through network pharmacology screening, GPAGAP had good drug-like properties, and 105 targets of GPAGAP overlap with diabetes mellitus type 2 (T2DM) targets. These targets were mainly enriched in the PI3K-Akt signaling pathway, TNF signaling pathway, IR and other signaling pathways related to T2DM. The results of IR-HepG2 cell model experiments showed that GPAGAP could reduce IR of HepG2 cells induced by high-glucose and high-insulin, and improve glucose consumption of IR-HepG2 cells. GPAGAP could increase the glycogen content, hexokinase (HK) and pyruvate kinase (PK) activities of IR-HepG2 cells, inhibit the accumulation of triglyceride (TG) and total cholesterol (TC) in IR-HepG2 cells, and enhance the activity of superoxide dismutase (SOD) in IR-HepG2 cells, reduce the content of malondialdehyde (MDA) and reactive oxygen species (ROS) in IR-HepG2 cells. The above results suggested that GPAGAP could through multi-target and multi-pathway to improve the glucose metabolism, lipid metabolism and oxidative stress response of IR-HepG2 cells. It has the potential effect of improving insulin resistance in T2DM.
Saeedi, P., Petersohn, I., Salpea, P., et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Research and Clinical Practice, 2019, 157: 107843. https://doi.org/10.1016/j.diabres.2019.107843
Nadia, L., James, B., Helen, P., et al. Type 2 diabetes in adolescents and young adults. Lancet Diabetes Endocrinol, 2018, 6: 69–80. https://doi.org/10.1016/S2213-8587(17)30186-9
Xu, W., Zhou, Y., Lin, L., et al. Hypoglycemic effects of black brick tea with fungal growth in hyperglycemic mice model. Food Science and Human Wellness, 2021, 11: 711–718. https://doi.org/10.1016/j.fshw.2021.12.028
Li, D., Zhu, Y., Wang, Y., et al. Perspectives on diacylglycerol-induced improvement of insulin sensitivity in type 2 diabetes. Food Science and Human Wellness, 2021, 2: 230–237. https://doi.org/10.1016/j.fshw.2021.11.004
Lin, Q., Yang, L., Han, L., et al. Effects of soy hull polysaccharide on dyslipidemia and pathoglycemia in rats induced by a high-fat-high-sucrose diet. Food Science and Human Wellness, 2021, 11: 49–57. https://doi.org/10.1016/j.fshw.2021.07.006
Harsch, I. A., Kaestner, R. H., Konturek, P. C. Hypoglycemic side effects of sulfonylureas and repaglinide in ageing patients-knowledge and self-management. Journal of Physiology and Pharmacology, 2018, 69: 647–649. https://doi.org/10.26402/jpp.2018.4.15
Zhang, Y., Wang, N., Wang, W., et al. Molecular mechanisms of novel peptides from silkworm pupae that inhibit α-glucosidase. Peptides, 2015, 76: 45–50. https://doi.org/10.1016/j.peptides.2015.12.004
Zhang, Y., Chen, R., Chen, X. L., et al. Dipeptidyl peptidase IV-inhibitory peptides derived from silver carp ( Hypophthalmichthys molitrix Val.) proteins. Journal of Agricultural and Food Chemistry, 2016, 64: 831–839. https://doi.org/10.1021/acs.jafc.5b05429
Zambrowicz, A., Eckert, E., Pokora, M., et al. Antioxidant and antidiabetic activities of peptides isolated from a hydrolysate of an egg-yolk protein by-product prepared with a proteinase from Asian pumpkin ( Cucurbita ficifolia). RSC Advances, 2015, 5: 10460–10467. https://doi.org/10.1039/c4ra12943a
Ramadhan, A. H., Nawas, T., Zhang, X. W., et al. Purification and identification of a novel antidiabetic peptide from Chinese giant salamander ( Andrias davidianus) protein hydrolysate against α-amylase and α-glucosidase. International Journal of Food Properties, 2018, 20: S3360–S3372. https://doi.org/10.1080/10942912.2017.1354885
Li, D., Wang, D., Yan, S. Exploration of underlying molecular mechanism of lycii cortex in treating type 2 diabetes mellitus based on network pharmacology and molecular docking. E3S Web of Conferences, 2021, 233: 02007. https://doi.org/10.1051/e3sconf/202123302007
Oh, K. K., Adnan, M., Cho, D. H. Active ingredients and mechanisms of Phellinus linteus (grown on Rosa multiflora) for alleviation of type 2 diabetes mellitus through network pharmacology. Gene, 2021, 768: 145320. https://doi.org/10.1016/j.gene.2020.145320
Zhang, J., Chen, Z., Zhang, L., et al. A systems-based analysis to explore the multiple mechanisms of Shan Zha for treating human diseases. Food Function, 2021, 12: 1176–1191. https://doi.org/10.1039/d0fo02433c
Yang, Q., Zhu, Z., Wang, L., et al. The protective effect of silk fibroin on high glucose induced insulin resistance in HepG2 cells. Environmental Toxicology and Pharmacology, 2019, 69: 66–71. https://doi.org/10.1016/j.etap.2019.04.001
Lee, A. Y., Park, W., Kang, T. W., et al. Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis. Journal of Ethnopharmacology, 2018, 221: 151159. https://doi.org/10.1016/j.jep.2018.04.027
Dominguez, E. A. T., Peñafiel, A. M., Pedraza, A. G., et al. Molecular mechanisms from insulin-mimetic effect of vitamin D: treatment alternative in type 2 diabetes mellitus. Food Function, 2021, 12: 6682–6690. https://doi.org/10.1039/d0fo03230a
Fan, X., Tao, J., Zhou, Y., et al. Investigations on the effects of ginsenoside-Rg1 on glucose uptake and metabolism in insulin resistant HepG2 cells. European Journal of Pharmacology, 2019, 843: 277–284. https://doi.org/10.1016/j.ejphar.2018.11.024
Zhou, K., Xiao, S., Cao, S., et al. Improvement of glucolipid metabolism and oxidative stress via modulating PI3K/Akt pathway in insulin resistance HepG2 cells by chickpea flavonoids. Food Chemistry-X, 2024, 23: 101630. https://doi.org/10.1016/j.fochx.2024.101630
Wang, K., Wang, H., Liu, Y., et al. Dendrobium officinale polysaccharide attenuates type 2 diabetes mellitus via the regulation of PI3K/Akt-mediated glycogen synthesis and glucose metabolism. Journal of Functional Foods, 2018, 40: 261–271. https://doi.org/10.1016/j.jff.2017.11.004
Cao, C., Li, C., Chen, Q., et al. Physicochemical characterization, potential antioxidant and hypoglycemic activity of polysaccharide from Sargassum pallidum. International Journal of Biological Macromolecules, 2019, 139: 1009–1017. https://doi.org/10.1016/j.ijbiomac.2019.08.069
Kojta, I., Chacińska, M., Zabielska, A. B. Obesity, bioactive lipids, and adipose tissue inflammation in insulin resistance. Nutrients, 2020, 12: 1305. https://doi.org/10.3390/nu12051305
Liu, L., Tang, D., Zhao, H. Q., et al. Hypoglycemic effect of the polyphenols rich extract from Rose rugosa Thunb on high fat diet and STZ induced diabetic rats. Journal of Ethnopharmacology, 2017, 200: 174–181. https://doi.org/10.1016/j.jep.2017.02.022
Prudente, S., Jungtrakoon, P., Marucci, A., et al. Loss-of-function mutations in APPL1 in familial diabetes mellitus. The American Journal of Human Genetics, 2015, 97: 177–185. https://doi.org/10.1016/j.ajhg.2015.05.011
Albury-Warren, T. M., Pandey, V., Spinel, L. P., et al. Prediabetes linked to excess glucagon in transgenic mice with pancreatic active AKT1. Journal of Endocrinology, 2016, 228: 49–59. https://doi.org/10.1530/JOE-15-0288
Maffei, A., Lembo, G., Carnevale, D. PI3Kinases in diabetes mellitus and its related complications. International Journal of Molecular Sciences, 2018, 19: 4098. https://doi.org/10.3390/ijms19124098
Tsay, A., Wang, J. C. The role of PIK3R1 in metabolic function and insulin sensitivity. International Journal of Molecular Sciences, 2023, 24: 12665. https://doi.org/10.3390/ijms241612665
Liu, J., Liu, J., Tong, X., et al. Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of Huai Hua San against ulcerative colitis. Drug Design, Development and Therapy, 2021, 15: 3255–3276. https://doi.org/10.2147/DDDT.S319786
Pan, Y., Wang, Y., Zhao, Y., et al. Inhibition of JNK phosphorylation by a novel curcumin analog prevents high glucose-induced inflammation and apoptosis in cardiomyocytes and the development of diabetic cardiomyopathy. Diabetes, 2014, 63: 3497–3511. https://doi.org/10.2337/db13-1577
Cao, Y., Sun, W., Xu, G. Fuzhu jiangtang granules combined with metformin reduces insulin resistance in skeletal muscle of diabetic rats via PI3K/Akt signaling. PharmBio, 2019, 57: 660–668. https://doi.org/10.1080/13880209.2019.1659831
Song, J. J., Wang, Q., Du, M., et al. Casein glycomacropeptide-derived peptide IPPKKNQDKTE ameliorates high glucose-induced insulin resistance in HepG2 cells via activation of AMPK signaling. Molecular Nutrition & Food Research, 2017, 61: 61. https://doi.org/10.1002/mnfr.201600301
Akash, M. S. H., Rehman, K., Liaqat, A. Tumor necrosis factor-alpha: role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. Journal of Cellular Biochemistry, 2018, 119: 105–110. https://doi.org/10.1002/jcb.26174
Long, M., Zhou, J., Li, D., et al. Long-term over-expression of neuropeptide Y in hypothalamic paraventricular nucleus contributes to adipose tissue insulin resistance partly via the Y5 receptor. PLoS One, 2015, 10: e0126714. https://doi.org/10.1371/journal.pone.0126714
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