Acknowledgement
This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2020R1A6A3A01100467, 2020M3A9E410438021). This work was also supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020R1F1A1073551).
References
- Cantley J, Ashcroft FM. Q&A: insulin secretion and type 2 diabetes: why do β-cells fail? BMC Biol 2015;13:1-7. https://doi.org/10.1186/s12915-014-0111-3
- Is Sobczak A, A Blindauer C, J Stewart A. Changes in plasma free fatty acids associated with type-2 diabetes. Nutrients 2019;11:2022.
- Newsholme P, Keane D, Welters HJ, Morgan NG. Life and death decisions of the pancreatic β-cell: the role of fatty acids. Clin. Sci. 2007;112:27-42. https://doi.org/10.1042/CS20060115
- Kharroubi I, Ladriere L, Cardozo AK, Dogusan Z, Cnop M, Eizirik DcL. Free fatty acids and cytokines induce pancreatic β-cell apoptosis by different mechanisms: role of nuclear factor-κB and endoplasmic reticulum stress. Endocrinology 2004;145:5087-96. https://doi.org/10.1210/en.2004-0478
- Oh YS, Bae GD, Baek DJ, Park EY, Jun HS. Fatty acid-induced lipotoxicity in pancreatic beta-cells during development of type 2 diabetes. Front. Endocrinol. 2018;9:384.
- Hirata T, Kawai T, Hirose H, Tanaka K, Kurosawa H, Fujii C, Fujita H, Seto Y, Matsumoto H, Itoh H. Palmitic acid-rich diet suppresses glucose-stimulated insulin secretion (GSIS) and induces endoplasmic reticulum (ER) stress in pancreatic islets in mice. Endocr. Res. 2016;41:8-15. https://doi.org/10.3109/07435800.2015.1038352
- Liang H, Zhong Y, Zhou S, Li QQ. Palmitic acid-induced apoptosis in pancreatic β-cells is increased by liver X receptor agonist and attenuated by eicosapentaenoate. Vivo 2011;25:711-8.
- Wang T, Sun P, Chen L, Huang Q, Chen K, Jia Q, Li Y, Wang H. Cinnamtannin D-1 protects pancreatic β-cells from palmitic acid-induced apoptosis by attenuating oxidative stress. J. Agric. Food Chem. 2014;62:5038-45. https://doi.org/10.1021/jf500387d
- Kimura M, Waki I, Chujo T, Kikuchi T, Hiyama C, Yamazaki K, Tanaka O. Effects of hypoglycemic components in ginseng radix on blood insulin level in alloxan diabetic mice and on insulin release from perfused rat pancreas. J. Pharmacobio-Dyn. 1981;4:410-7. https://doi.org/10.1248/bpb1978.4.410
- Su CF, Cheng JT, Liu IM. Increase of acetylcholine release by Panax ginseng root enhances insulin secretion in Wistar rats. Neurosci. Lett. 2007;412:101-4. https://doi.org/10.1016/j.neulet.2006.10.044
- Kim K, Kim HY. Korean red ginseng stimulates insulin release from isolated rat pancreatic islets. J. Ethnopharmacol 2008;120:190-5. https://doi.org/10.1016/j.jep.2008.08.006
- Bai L, Gao J, Wei F, Zhao J, Wang D, Wei J. Therapeutic potential of ginsenosides as an adjuvant treatment for diabetes. Front. Pharmacol. 2018;9:423.
- Kim YJ, Park SM, Jung HS, Lee EJ, Kim TK, Kim TN, Kwon MJ, Lee SH, Rhee BD, Kim Mk. Ginsenoside Rg3 prevents INS-1 cell death from intermittent high glucose stress. Islets 2016;8:57-64. https://doi.org/10.1080/19382014.2016.1161874
- Chen F, Chen Y, Kang X, Zhou Z, Zhang Z, Liu D. Anti-apoptotic function and mechanism of ginseng saponins in Rattus pancreatic β-cells. Biol. Pharm. Bull. 2012;35:1568-73. https://doi.org/10.1248/bpb.b12-00461
- Kim KS, Yang HJ, Lee IS, Kim KH, Park J, Jeong HS, Kim Y, Ahn KS, Na YC, Jang HJ. The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice. Sci. Rep. 2015;5:1-12. https://doi.org/10.1038/srep18325
- Kim K, Kim DH, Kim YH. Compound K protects MIN6N8 pancreatic β-cells against palmitate-induced apoptosis through modulating SAPK/JNK activation. Cell Biol. Int. 2010;34:75-80. https://doi.org/10.1042/CBI20090020
- Gu J, Li W, Xiao D, Wei S, Cui W, Chen W, Hu Y, Bi X, Kim Y, Li J. Compound K, a final intestinal metabolite of ginsenosides, enhances insulin secretion in MIN6 pancreatic β-cells by upregulation of GLUT2. Fitoterapia 2013;87:84-8. https://doi.org/10.1016/j.fitote.2013.03.020
- Kim KS, Yang HJ, Lee IS, Kim KH, Park J, Jeong HS, Kim Y, Ahn KS, Na YC, Jang HJ. The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice. Sci. Rep. 2015;5:1-12. https://doi.org/10.1038/srep18325
- Jin HR, Du CH, Wang CZ, Yuan CS, Du W. Ginseng metabolite protopanaxadiol interferes with lipid metabolism and induces endoplasmic reticulum stress and p53 activation to promote cancer cell death. Phytother. Res. 2019;33:610-7. https://doi.org/10.1002/ptr.6249
- Kim JE, Jang IS, Sung BH, Kim SC, Lee JY. Rerouting of NADPH synthetic pathways for increased protopanaxadiol production in Saccharomyces cerevisiae. Sci. Rep. 2018;8:1-11. https://doi.org/10.1038/s41598-018-34210-3
- Sun J, Hu S, Song X. Adjuvant effects of protopanaxadiol and protopanaxatriol saponins from ginseng roots on the immune responses to ovalbumin in mice. Vaccine 2007;25:1114-20. https://doi.org/10.1016/j.vaccine.2006.09.054
- Wang CZ, Zhang Z, Wan JY, Zhang CF, Anderson S, He X, Yu C, He TC, Qi LW, Yuan CS. Protopanaxadiol, an active ginseng metabolite, significantly enhances the effects of fluorouracil on colon cancer. Nutrients 2015;7:799-814. https://doi.org/10.3390/nu7020799
- Shoaib RM, Ahmad KA, Wang YX. Protopanaxadiol alleviates neuropathic pain by spinal microglial dynorphin A expression following glucocorticoid receptor activation. Br. J. Pharmacol. 2021;178:2976-97. https://doi.org/10.1111/bph.15471
- Lupi R, Del Guerra S, Marselli L, Bugliani M, Boggi U, Mosca F, Marchetti P, Del Prato S. Rosiglitazone prevents the impairment of human islet function induced by fatty acids: evidence for a role of PPARγ2 in the modulation of insulin secretion. Am. J. Physiol. - Endocrinol. Metab. 2004;286:E560-7. https://doi.org/10.1152/ajpendo.00561.2002
- Guan FY, Gu J, Li W, Zhang M, Ji Y, Li J, Chen L, Hatch GM. Compound K protects pancreatic islet cells against apoptosis through inhibition of the AMPK/JNK pathway in type 2 diabetic mice and in MIN6 β-cells. Life Sciences 2014;107:42-9. https://doi.org/10.1016/j.lfs.2014.04.034
- Kim K, Park M, Kim HY. Ginsenoside Rg3 suppresses palmitate-induced apoptosis in MIN6N8 pancreatic β-cells. J. Clin. Biochem. 2009;46:30-5. https://doi.org/10.3164/jcbn.09-49
- Gwak YS, Han JY, Choi YE. Production of ginsenoside aglycone (protopanaxatriol) and male sterility of transgenic tobacco co-overexpressing three Panax ginseng genes: PgDDS, CYP716A47, and CYP716A53v2. J. Ginseng Res. 2019;43:261-71. https://doi.org/10.1016/j.jgr.2018.02.005
- Shin JH, Park YJ, Kim W, Kim DO, Kim BY, Lee H, Baik MY. Change of ginsenoside profiles in processed ginseng by drying, steaming, and puffing. J Microbiol Biotechn 2019;29:222-9. https://doi.org/10.4014/jmb.1809.09056
- Park MW, Ha J, Chung SH. 20 (S)-ginsenoside Rg3 enhances glucose-stimulated insulin secretion and activates AMPK. Biol. Pharm. Bull. 2008;31:748-51. https://doi.org/10.1248/bpb.31.748
- Han GC, Ko SK, Sung JH, Chung SH. Compound K enhances insulin secretion with beneficial metabolic effects in db/db mice. J. Agric. Food Chem. 2007;55:10641-8. https://doi.org/10.1021/jf0722598
- Ahn JH, Kim MH, Kwon HJ, Choi SY, Kwon HY. Protective effects of oleic acid against palmitic acid-induced apoptosis in pancreatic AR42J cells and its mechanisms. Korean J Physiol Pharmacol 2013;17:43-50. https://doi.org/10.4196/kjpp.2013.17.1.43
- Wu J, Wu JJ, Yang LJ, Wei LX, Zou DJ. Rosiglitazone protects against palmitate-induced pancreatic beta-cell death by activation of autophagy via 5'-AMP-activated protein kinase modulation. Endocrine 2013;44:87-98. https://doi.org/10.1007/s12020-012-9826-5
- Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM: genetic and clinical implications. Diabetes 1995;44:863-70. https://doi.org/10.2337/diab.44.8.863
- Shimabukuro M, Wang MY, Zhou YT, Newgard CB, Unger RH. Protection against lipoapoptosis of β cells through leptin-dependent maintenance of Bcl-2 expression. Proc. Natl. Acad. Sci. 1998;95:9558-61. https://doi.org/10.1073/pnas.95.16.9558
- Zhang M, Yang C, Zhu M, Qian L, Luo Y, Cheng H, Geng R, Xu X, Qian C, Liu Y. Saturated fatty acids entrap PDX1 in stress granules and impede islet beta cell function. Diabetologia 2021;64:1144-57. https://doi.org/10.1007/s00125-021-05389-4
- Brissova M, Shiota M, Nicholson WE, Gannon M, Knobel SM, Piston DW, Wright CV, Powers AC. Reduction in pancreatic transcription factor PDX-1 impairs glucose-stimulated insulin secretion. J. Biol. Chem 2002;277:11225-32. https://doi.org/10.1074/jbc.M111272200
- Li L, Sun Y, Zhang Y, Wang W, Ye C. Mutant huntingtin impairs pancreatic β-cells by recruiting IRS-2 and disturbing the PI3K/AKT/FoxO1 signaling pathway in huntington's disease. J. Mol. Neurosci. 2021;71:2646-58. https://doi.org/10.1007/s12031-021-01869-9
- Liu S, Li X, Wu Y, Duan R, Zhang J, Du F, Zhang Q, Li Y, Li N. Effects of vaspin on pancreatic β cell secretion via PI3K/Akt and NF-κB signaling pathways. PLoS One 2017;12:e0189722.
- Dai L, Liu KF, Si CL, Wang LY, Liu J, He J, Lei JD. Ginsenoside nanoparticle: a new green drug delivery system. J Mater Chem B 2016;4:529-38. https://doi.org/10.1039/C5TB02305J
- Niu T, Smith DL, Yang Z, Gao S, Yin TJ, Jiang ZH, You M, Gibbs RA, Petrosino JF, Hu M. Bioactivity and bioavailability of ginsenosides are dependent on the glycosidase activities of the A/J mouse intestinal microbiome defined by pyrosequencing. Pharm Res-Dordr 2013;30:836-46. https://doi.org/10.1007/s11095-012-0925-z
- Leung KW, Wong AS. Pharmacology of ginsenosides: a literature review. Chin Med 2010;5:20.
- Pan WL, Xue BL, Yang CL, Miao LL, Zhou LL, Chen QY, Cai Q, Liu Y, Liu DC, He HB, et al. Biopharmaceutical characters and bioavailability improving strategies of ginsenosides. Fitoterapia 2018;129:272-82. https://doi.org/10.1016/j.fitote.2018.06.001