Journal of Zhejiang University-SCIENCE B

, Volume 19, Issue 7, pp 559–569 | Cite as

Stability of a type 2 diabetes rat model induced by high-fat diet feeding with low-dose streptozotocin injection

  • Xiao-xuan Guo
  • Yong Wang
  • Kai Wang
  • Bao-ping Ji
  • Feng ZhouEmail author



The present study aims at determining the stability of a popular type 2 diabetes rat model induced by a high-fat diet combined with a low-dose streptozotocin injection.


Wistar rats were fed with a high-fat diet for 8 weeks followed by a one-time injection of 25 or 35 mg/kg streptozotocin to induce type 2 diabetes. Then the diabetic rats were fed with regular diet/high-fat diet for 4 weeks. Changes in biochemical parameters were monitored during the 4 weeks.


All the rats developed more severe dyslipidemia and hepatic dysfunction after streptozotocin injection. The features of 35 mg/kg streptozotocin rats more resembled type 1 diabetes with decreased body weight and blood insulin. Rats with 25 mg/kg streptozotocin followed by normal diet feeding showed normalized blood glucose level and pancreatic structure, indicating that normal diet might help recovery from certain symptoms of type 2 diabetes. In comparison, diabetic rats fed with high-fat diet presented decreased but relatively stable blood glucose level, and this was significantly higher than that of the control group (P>0.05).


This model easily recovers with normal diet feeding. A high-fat diet is suggested as the background diet in future pharmacological studies using this model.

Key words

High-fat diet Stability Streptozotocin Type 2 diabetes mellitus 




探讨高脂饮食联合低剂量链脲佐菌素(STZ)造 大鼠二型糖尿病模型在不同饮食背景下的稳定 性。


首次探讨在正常饮食和高脂饮食的背景下,该常 见的大鼠二型糖尿病模型的稳定性。可为造模后 期干预阶段的饲料选择提供依据。


饲喂Wistar 大鼠高脂饮食8 周后,注射25 或 35 mg/kg STZ 来诱导二型糖尿病。之后每组分别 饲喂正常饲料和高脂饲料4 周,检测血液生化指 标的稳定性。


不管在何种饮食下,糖尿病大鼠都出现了空腹血 糖显著恢复,血脂紊乱加剧的现象。其中35 mg/kg STZ 注射组大鼠的特征更接近一型糖尿病,而 25 mg/kg STZ 注射组大鼠表现出二型糖尿病的特 征。相比高脂饮食,正常饮食更容易导致空腹血 糖和胰岛结构的恢复。因此,在正常饮食下该模 型稳定性欠佳,在后期的药理学实验中推荐使用 高脂饮食。


高脂饮食 稳定性 链脲佐菌素 二型糖尿病 

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  1. Bhattacharya S, Dey D, Roy SS, 2007. Molecular mechanism of insulin resistance. J Biosci, 32(2):405–413. Scholar
  2. Bibak B, Khalili M, Rajaei Z, et al., 2014. Effects of melatonin on biochemical factors and food and water consumption in diabetic rats. Adv Biomed Res, 3(1):173. Scholar
  3. Garg A, Misra A, 2002. Hepatic steatosis, insulin resistance, and adipose tissue disorders. J Clin Endocrinol Metab, 87(7):3019–3022. Scholar
  4. Hotamisligil GS, Shargill NS, Spiegelman BM, 1993. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science, 259(5091):87–91. Scholar
  5. Institute of Laboratory Animal Resources Committee, 1996. Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington DC.Google Scholar
  6. Ji J, Zhang C, Luo X, et al., 2015. Effect of stay-green wheat, a novel variety of wheat in China, on glucose and lipid metabolism in high-fat diet induced type 2 diabetic rats. Nutrients, 7(7):5143–5155. Scholar
  7. Lee JS, Son HS, Maeng YS, et al., 1994. Effects of buckwheat on organ weight, glucose and lipid metabolism in streptozotocin-induced diabetic rats. J Korean Soc Food Sci Nutr, 27(8):819–827.Google Scholar
  8. Leedom LJ, Meehan WP, 1989. The psychoneuroendocrinology of diabetes mellitus in rodents. Psychoneuroendocrinology, 14(4):275–294. Scholar
  9. Liu J, Zhang H, Ji B, et al., 2014. A diet formula of Puerariae radix, Lycium barbarum, Crataegus pinnatifida, and Polygonati rhizoma alleviates insulin resistance and hepatic steatosis in CD-1 mice and HepG2 cells. Food Funct, 5(5):1038–1049. Scholar
  10. Luo J, Quan J, Tsai J, et al., 1998. Nongenetic mouse models of non-insulin-dependent diabetes mellitus. Metabolism, 47(6):663–668. Scholar
  11. Mahmoud AM, Ashour MB, Abdel-Moneim A, et al., 2012. Hesperidin and naringin attenuate hyperglycemiamediated oxidative stress and proinflammatory cytokine production in high fat fed/streptozotocin-induced type 2 diabetic rats. J Diabetes Complications, 26(6):483–490. Scholar
  12. Mansor LS, Gonzalez ER, Cole MA, et al., 2013. Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin. Cardiov Diabetol, 12(1):136. Scholar
  13. Marx JL, 1979. The HDL: the good cholesterol carriers? Science, 205(4407):677–679.CrossRefPubMedGoogle Scholar
  14. Rathmann W, Giani G, 2004. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care, 27(10):2568–2569. Scholar
  15. Reed M, Meszaros K, Entes L, et al., 2000. A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism, 49(11):1390–1394. Scholar
  16. Rossmeisl M, Rim JS, Koza RA, et al., 2003. Variation in type 2 diabetes-related traits in mouse strains susceptible to diet-induced obesity. Diabetes, 52(8):1958–1966. Scholar
  17. Sahin K, Onderci M, Tuzcu M, et al., 2007. Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus: the fat-fed, streptozotocintreated rat. Metabolism, 56(9):1233–1240. Scholar
  18. Schnedl WJ, Ferber S, Johnson JH, et al., 1994. STZ transport and cytotoxicity: specific enhancement in GLUT2-expressing cells. Diabetes, 43(11):1326–1333.CrossRefPubMedGoogle Scholar
  19. Shafrir E, 2003. Diabetes in animals: contribution to the understanding of diabetes by study of its etiopathology in animal models. In: Porte D, Sherwin RS, Baron A (Eds.), Diabetes Mellitus. McGraw-Hill, New York.Google Scholar
  20. Shatwan IA, Ahmed LA, Badkook MM, 2013. Effect of barley flour, crude cinnamon, and their combination on glycemia, dyslipidemia, and adipose tissue hormones in type 2 diabetic rats. J Med Food, 16(7):656–662. Scholar
  21. Shaw JE, Sicree RA, Zimmet PZ, 2010. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract, 87(1):4–14. Scholar
  22. Siri-Tarino PW, Sun Q, Hu FB, et al., 2010. Saturated fatty acids and risk of coronary heart disease: modulation by replacement nutrients. Curr Atherosclerosis Rep, 12(6): 384–390. Scholar
  23. Srinivasan K, Viswanad B, Asrat L, et al., 2005. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: a model for type 2 diabetes and pharmacological screening. Pharmacol Res, 52(4):313–320. Scholar
  24. Tan BKH, Tan CH, Pushparaj PN, 2005. Anti-diabetic activity of the semi-purified fractions of Averrhoa bilimbi in high fat diet fed-streptozotocin-induced diabetic rats. Life Sci, 76(24):2827–2839. Scholar
  25. Vinson JA, Zhang J, 2005. Black and green teas equally inhibit diabetic cataracts in a streptozotocin-induced rat model of diabetes. J Agric Food Chem, 53(9):3710–3713. Scholar
  26. Wang C, Li J, Lv X, et al., 2009. Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin. Eur J Pharmacol, 620(1-3):131–137. Scholar
  27. Wang O, Liu J, Cheng Q, et al., 2015. Effects of ferulic acid and γ-oryzanol on high-fat and high-fructose diet-induced metabolic syndrome in rats. PLoS ONE, 10(2):e0118135. Scholar
  28. Wang Y, Campbell T, Perry B, et al., 2011. Hypoglycemic and insulin-sensitizing effects of berberine in high-fat dietand streptozotocin-induced diabetic rats. Metabolism, 60(2):298–305. Scholar
  29. Watts LM, Manchem VP, Leedom TA, et al., 2005. Reduction of hepatic and adipose tissue glucocorticoid receptor expression with antisense oligonucleotides improves hyperglycemia and hyperlipidemia in diabetic rodents without causing systemic glucocorticoid antagonism. Diabetes, 54(6):1846–1853. Scholar
  30. Zhang L, Yang J, Chen X, et al., 2010. Antidiabetic and antioxidant effects of extracts from Potentilla discolor Bunge on diabetic rats induced by high fat diet and streptozotocin. J Ethnopharmacol, 132(2):518–524. Scholar

Copyright information

© Zhejiang University and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Beijing Key Laboratory of Functional Food from Plant Resources, College of Food Science and Nutritional EngineeringChina Agricultural UniversityBeijingChina
  2. 2.Academy of State Administration of GrainBeijingChina
  3. 3.Institute of Apicultural ResearchChinese Academy of Agricultural SciencesBeijingChina

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