DOI QR코드

DOI QR Code

Effects of autumn olive berry on insulin resistance and hyperglycemia in mice fed a high-fat, high-sucrose diet

고지방·고단순당 식이 섭취 마우스에서 토종보리수 열매의 인슐린 저항성 및 고혈당 개선 효과

  • Ha-Neul Choi (Department of Food and Nutrition, Changwon National University) ;
  • Ae-Jin Jo (Department of Nutrition, Inje University, Haeundae Paik Hospital) ;
  • Ha-Na Kim (Department of Digital Anti-aging Healthcare, Inje University) ;
  • Jung-In Kim (Department of Digital Anti-aging Healthcare, Inje University)
  • 최하늘 (창원대학교 식품영양학과) ;
  • 조애진 (인제대학교 해운대백병원 영양팀) ;
  • 김하나 (인제대학교 디지털항노화헬스케어학과) ;
  • 김정인 (인제대학교 디지털항노화헬스케어학과)
  • Received : 2023.12.05
  • Accepted : 2024.01.11
  • Published : 2024.02.28

Abstract

Purpose: Type 2 diabetes mellitus is a metabolic condition marked by persistent elevated blood sugar levels resulting from insulin resistance. The effective management of diabetes mellitus involves strict regulation of the blood glucose levels. This study examined the effects of Autumn olive (Elaeagnus umbellata Thunb.) berry (AOB) on insulin resistance and hyperglycemia using a type 2 diabetes mellitus animal model. Methods: Eight-week-old C57BL/6J mice were divided into four groups. The control group received a basal diet, while the high-fat, high-sucrose (HFHS) group was fed a HFHS diet containing 27% sucrose and 33% lard for 12 weeks. The low AOB (LAOB) and high AOB (HAOB) groups were offered a HFHS diet with a 0.5% and 1.0% AOB extract, respectively. Results: The HAOB group showed significantly lower epididymal fat pad weight than the HFHS group. The LAOB and HAOB groups showed lower serum glucose levels and homeostasis model assessment for insulin resistance values than the HFHS group, and the HAOB group has lower serum insulin levels than the HFHS group. Supplementation with HAOB decreased serum cholesterol levels significantly compared with the HFHS group. The consumption of LAOB and HAOB reduced the serum triglyceride and hepatic total lipids and triglyceride levels compared to the HFHS group. In addition, LAOB and HAOB consumption in mice fed a HFHS diet increased adenosine monophosphate-activated protein kinase protein expression. Insulin receptor substrate-2 protein expression in the HAOB group was significantly higher than the HFHS group. Conclusion: AOB can alleviate hyperglycemia in type 2 diabetes mellitus partly by mitigating insulin resistance.

토종보리수 열매의 항당뇨 효과를 규명하기 위하여, 마우스를 네 군으로 나누어, 기본 식이, 고지방·고단순당 식이, 토종보리수 열매 추출물을 저농도 (0.5%) 및 고농도 (1.0%)로 첨가한 고지방·고단순당 식이를 12주간 제공하였다. 고지방·고단순당 식이를 섭취한 군은 대조군에 비해 체중 및 체중 증가량, 부고환 지방무게가 유의적으로 증가하였으나, 고농도 보리수 열매 추출물의 급여는 부고환 지방무게를 유의적으로 감소시켰다. 고지방·고단순당군은 대조군에 비해 혈당, 인슐린, HOMA-IR값이 유의적으로 증가하였으나, 고농도 보리수 열매 추출물은 인슐린 농도를 감소시켰고, 저농도 및 고농도 추출물은 혈당 및 HOMA-IR값을 감소시켰다. 고지방·고단순당군은 대조군에 비해 IRS-2 및 AMPK 단백질 발현도가 유의적으로 감소하였으나, 고농도 보리수 열매 추출물의 급여는 IRS-2 발현도를 증가시켰고, 저농도 및 고농도 보리수 열매 추출물의 급여는 AMPK 발현도를 증가시켰다. 따라서, 토종보리수 열매는 제2형 당뇨병 동물에서 인슐린 저항성을 개선시켜 고혈당 개선효과를 나타낸 것으로 나타났다. 고지방·고단순당 식이를 섭취한 마우스에서 저농도 및 고농도 토종보리수 열매 추출물의 급여는 혈청 중성지방 농도 및 간조직의 총 지질과 중성지방 함량을 감소시켰고, 고농도추출물의 급여는 혈청 콜레스테롤 농도를 감소시켜, 토종보리수 열매는 지방간과 이상지질혈증 개선효과를 나타내었다.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2016R1D1A3B03930584).

References

  1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2011; 34 Suppl 1(Suppl 1): S62-S69. https://doi.org/10.2337/dc11-S062
  2. Lovic D, Piperidou A, Zografou I, Grassos H, Pittaras A, Manolis A. The growing epidemic of diabetes mellitus. Curr Vasc Pharmacol 2020; 18(2): 104-109. https://doi.org/10.2174/1570161117666190405165911
  3. Prasad M, Rajagopal P, Devarajan N, Veeraraghavan VP, Palanisamy CP, Cui B, et al. A comprehensive review on high -fat diet-induced diabetes mellitus: an epigenetic view. J Nutr Biochem 2022; 107: 109037.
  4. Lebovitz HE. Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes 2001; 109 Suppl 2: S135-S148. https://doi.org/10.1055/s-2001-18576
  5. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 1999; 104(6): 787-794. https://doi.org/10.1172/JCI7231
  6. Matsuzaka T, Shimano H. New perspective on type 2 diabetes, dyslipidemia and non-alcoholic fatty liver disease. J Diabetes Investig 2020; 11(3): 532-534. https://doi.org/10.1111/jdi.13258
  7. Mooradian AD. Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab 2009; 5(3): 150-159. https://doi.org/10.1038/ncpendmet1066
  8. Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol 2009; 53(5 Suppl): S35-S42. https://doi.org/10.1016/j.jacc.2008.09.055
  9. Chamberlain JJ, Rhinehart AS, Shaefer CF Jr, Neuman A. Diagnosis and management of diabetes: synopsis of the 2016 American Diabetes Association standards of medical care in diabetes. Ann Intern Med 2016; 164(8): 542-552. https://doi.org/10.7326/M15-3016
  10. Lazarte J, Hegele RA. Dyslipidemia management in adults with diabetes. Can J Diabetes 2020; 44(1): 53-60. https://doi.org/10.1016/j.jcjd.2019.07.003
  11. Levetan C. Oral antidiabetic agents in type 2 diabetes. Curr Med Res Opin 2007; 23(4): 945-952. https://doi.org/10.1185/030079907X178766
  12. Agrawal N, Sharma M, Singh S, Goyal A. Recent advances of α-glucosidase inhibitors: a comprehensive review. Curr Top Med Chem 2022; 22(25): 2069-2086. https://doi.org/10.2174/1568026622666220831092855
  13. Pei R, Yu M, Bruno R, Bolling BW. Phenolic and tocopherol content of autumn olive (Elaeagnus umbellate) berries. J Funct Foods 2015; 16: 305-314. https://doi.org/10.1016/j.jff.2015.04.028
  14. Gamba G, Donno D, Mellano MG, Riondato I, Biaggi MD, Randriamampionona D, et al. Phytochemical characterization and bioactivity evaluation of autumn olive (Elaeagnus umbellata Thunb.) pseudodrupes as potential sources of health-promoting compounds. Appl Sci 2020; 10(12): 4354.
  15. Fordham IM, Clevidence BA, Wiley ER, Zimmerman RH. Fruit of autumn olive: a rich source of lycopene. HortScience 2001; 36(6): 1136-1137. https://doi.org/10.21273/HORTSCI.36.6.1136
  16. Khattak KF. Free radical scavenging activity, phytochemical composition and nutrient analysis of Elaeagnus umbellata berry. J Med Plants Res 2012; 6(39): 5196-5203. https://doi.org/10.5897/JMPR11.1128
  17. Kim JI, Baek HJ, Han DW, Yun JA. Autumn olive (Elaeagnus umbellata Thunb.) berry reduces fasting and postprandial glucose levels in mice. Nutr Res Pract 2019; 13(1): 11-16. https://doi.org/10.4162/nrp.2019.13.1.11
  18. Matthews DR, Hosker JP, Rudenski AS, Naykir BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28(7): 412-419. https://doi.org/10.1007/BF00280883
  19. Folch J, Lees M, Sloane Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957; 226(1): 497-509. https://doi.org/10.1016/S0021-9258(18)64849-5
  20. Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN. Diet-induced type II diabetes in C57BL/6J mice. Diabetes 1988; 37(9): 1163-1167. https://doi.org/10.2337/diab.37.9.1163
  21. Yang ZH, Miyahara H, Takeo J, Katayama M. Diet high in fat and sucrose induces rapid onset of obesity-related metabolic syndrome partly through rapid response of genes involved in lipogenesis, insulin signalling and inflammation in mice. Diabetol Metab Syndr 2012; 4(1): 32. https://doi.org/10.1186/1758-5996-4-32
  22. Choi HN, Kang MJ, Lee SJ, Kim JI. Ameliorative effect of myricetin on insulin resistance in mice fed a high-fat, high-sucrose diet. Nutr Res Pract 2014; 8(5): 544-549. https://doi.org/10.4162/nrp.2014.8.5.544
  23. Kim JI, Jo AJ, Yun JA, Han DW, Baek HJ. Composition for preventing and treating of obesity or metabolic disease comprising Elaeagnus umbellata extracts. Korea patent KR 10-2110040. 2020 May 12.
  24. Lunagariya NA, Patel NK, Jagtap SC, Bhutani KK. Inhibitors of pancreatic lipase: state of the art and clinical perspectives. EXCLI J 2014; 13: 897-921.
  25. Kim JY, Lee YS, Park EJ, Lee HJ. Honeysuckle berry (Lonicera caerulea L.) inhibits lipase activity and modulates the gut microbiota in high-fat diet-fed mice. Molecules 2022; 27(15): 4731.
  26. Lebovitz HE. α-Glucosidase inhibitors as agents in the treatment of diabetes. Diabetes Res 1998; 6: 132-145.
  27. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005; 26(3): 439-451. https://doi.org/10.1210/er.2005-0005
  28. Khalid M, Alkaabi J, Khan MA, Adem A. Insulin signal transduction perturbations in insulin resistance. Int J Mol Sci 2021; 22(16): 8590.
  29. Viollet B, Lantier L, Devin-Leclerc J, Hebrard S, Amouyal C, Mounier R, et al. Targeting the AMPK pathway for the treatment of Type 2 diabetes. Front Biosci (Landmark Ed) 2009; 14(9): 3380-3400. https://doi.org/10.2741/3460
  30. Perkins-Veazie PM, Black BL, Fordham IM, Howard LR. Lycopene and total phenol content of autumn olive (Elaeagnus umbellata) selections. HortScience 2005; 40(30): 883-893. https://doi.org/10.21273/HORTSCI.40.3.883f
  31. Cordero-Herrera I, Martin MA, Bravo L, Goya L, Ramos S. Cocoa flavonoids improve insulin signalling and modulate glucose production via AKT and AMPK in HepG2 cells. Mol Nutr Food Res 2013; 57(6): 974-985. https://doi.org/10.1002/mnfr.201200500
  32. Sadi G, Pektas MB, Koca HB, Tosun M, Koca T. Resveratrol improves hepatic insulin signaling and reduces the inflammatory response in streptozotocin-induced diabetes. Gene 2015; 570(2): 213-220. https://doi.org/10.1016/j.gene.2015.06.019
  33. Hirano T. Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb 2018; 25(9): 771-782. https://doi.org/10.5551/jat.RV17023
  34. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004; 114(2): 147-152. https://doi.org/10.1172/JCI200422422
  35. Zhang S, Xu M, Zhang W, Liu C, Chen S. Natural polyphenols in metabolic syndrome: protective mechanisms and clinical applications. Int J Mol Sci 2021; 22(11): 6110.
  36. Banach M, Surma S, Reiner Z, Katsiki N, Penson PE, Fras Z, et al. Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach (2022). Cardiovasc Diabetol 2022; 21(1): 263.
  37. Yang XH, Tu QM, Li L, Guo YP, Wang NS, Jin HM. Triglyceride-lowering therapy for the prevention of cardiovascular events, stroke, and mortality in patients with diabetes: a meta-analysis of randomized controlled trials. Atherosclerosis 2023: 117187.
  38. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993; 16(2): 434-444. https://doi.org/10.2337/diacare.16.2.434