doi:

DOI: 10.3724/SP.J.1141.2013.02108

Zoological Research (动物学研究) 2013/34:2 PP.108-115

Streptozotocin induction of type 2 diabetes in tree shrew


Abstract:
The aim of this study was to induce type 2 diabetes in tree shrew (Tupaia belangeri chinensis). Streptozotocin (STZ), a glucosamine derivative of nitrosourea and preferentially toxic to pancreatic beta cells, has been commonly used to induce type 1 and 2 diabetes in experimental animals. Tree shrews were treated with different low doses of STZ (60, 70, and 80 mg/kg), with six control tree shrews receiving citrate buffer. After STZ injection, tree shrews displayed increased fasting blood and urine glucose, impaired oral glucose tolerance test, and disturbed lipids metabolism and renal function. However, STZ induced tree shrews showed no diabetic complications such as diabetic lactic acidosis and hyperglycemic hyperosmolar. Animals with the above type 2 diabetic-like symptoms were variable across the three groups from 66.7% to 100%, and mortality ranged from 16.7% to 33.3%. Thus, two 80 mg/kg STZ dose injections were appeared more appropriate than other doses to induce tree shrew model of type 2 diabetes. Our results demonstrated that type 2 diabetes could be induced with favorable STZ application in tree shrew.

Key words:Tree shrew,Type 2 diabetes,Streptozotocin

ReleaseDate:2015-04-16 19:34:18



Chinese Diabetes Society. 2011. Chinese Guideline for Type 2 Diabetes. Beijing: Peking University Medical Press. [中华医学会糖尿病学分会. 2011. 中国2型糖尿病防治指南. 北京: 北京大学医学出版社.]

Deeds MC, Anderson JM, Armstrong AS, Gastineau DA, Hiddinga HJ, Jahangir A, Eberhardt NL, Kudva YC. 2011. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Laboratory Animals, 45(3): 131-140.

Erdal N, Gurgul S, Kavak S, Yildiz A, Emre M. 2011. Deterioration of bone quality by streptozotocin (STZ)-induced type 2 diabetes mellitus in rats. Biological Trace Element Research, 140(3): 342-353.

Fuchs E. 1999. Tree shrews. In: Poole T, editor. UFAW handbook on the care and management of laboratory animals, vol. 1, 7th ed. Terrestrial vertebrates. Oxford: Blackwell. 235–245.

Goldberg IJ. 2001. Clinical review 124: Diabetic dyslipidemia: causes and consequences. Journal of Clinical Endocrinology and Metabolism, 86(3): 965-971.

Ishiko S, Yoshida A, Mori F, Abiko T, Kitaya N, Kojima M, Saito K. 1997. Early ocular changes in a tree shrew model of diabetes. Nippon Ganka Gakkai Zasshi, 101(1): 19-23.

Junod A, Lambert AE, Stauffacher W, Renold AE. 1969. Diabetogenic action of streptozotocin: relationship of dose to metabolic response. Journal of Clinical Investigation, 48(11): 2129-2139.

Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, Renold AE. 1967. Studies of the diabetogenic action of streptozotocin. Proceedings of the Society for Experimental Biology and Medicine, 126(1): 201-205.

Kavanagh K, Flynn DM, Nelson C, Zhang L, Wagner JD. 2011. Characterization and validation of a streptozotocin-induced diabetes model in the vervet monkey. Journal of Pharmacological and Toxicological Methods, 63(3): 296-303.

Kolb H, Kröncke KD. 1993. IDDM: lessons from the low-dose streptozotocin model in mice. Diabetes Reviews, 1: 116-126.

Koulmanda M, Qipo A, Chebrolu S, O'Neil J, Auchincloss H, Smith RN. 2003. The effect of low versus high dose of streptozotocin in cynomolgus monkeys (Macaca fascilularis). American Journal of Transplantation, 3(3): 267-272.

Kramer J, Moeller EL, Hachey A, Mansfield KG, Wachtman LM. 2009. Differential expression of GLUT2 in pancreatic islets and kidneys of New and Old World nonhuman primates. American Journal of Physiology Regulatory Integrative and Comparative Physiology, 296(3): R786-R793.

Kuttler B, Schneider E. 1982. Diabetes mellitus in mice induced by multiple subdiabetogenic doses of streptozotocin: age and sex dependence. Acta Biologica et Medica Germanica, 41(12): 1199-1202.

Li HY. 2010. A Study on Artificial Induced Type 2 Diabetes Mellitus Animal Models in Tree Shrews. Mastre's Degree thesis, Chinese Academy of Medical Sciences, Peking Union Medical College. [李海燕. 2010. 人工诱导树鼩2型糖尿病动物模型的研究. 硕士学位论文, 中国医学科学院, 北京协和医学院.]

Nain P, Saini V, Sharma S, Nain J. 2012. Antidiabetic and antioxidant potential of Emblica officinalis Gaertn. leaves extract in streptozotocin-induced type-2 diabetes mellitus (T2DM) rats. Journal of Ethnopharmacology, 142(1): 65-71.

Palm F, Ortsäter H, Hansell P, Liss P, Carlsson PO. 2004. Differentiating between effects of streptozotocin per se and subsequent hyperglycemia on renal function and metabolism in the streptozotocin-diabetic rat model. Diabetes Metabolism Research and Reviews, 20(6): 452-459.

Rabb GB, Getty RE, Williamson WM, Lombard LS. 1966. Spontaneous diabetes mellitus in tree shrews, Urogale everetti. Diabetes, 15(5): 327-330.

Rasch R. 1979. Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Kidney size and glomerular volume. Diabetologia, 16(2): 125-128.

Rasch R. 1980. Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment. Albumin excretion. Diabetologia, 18(5): 413-416.

Rerup CC. 1970. Drugs producing diabetes through damage of the insulin secreting cells. Pharmacological Reviews, 22(4): 485-518. Shaw JE, Sicree RA, Zimmet PZ. 2010. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Research and Clinical Practice, 87(1): 4-14.

Shepherd J. 1994. Diabetic dyslipidemia andatherosclerosis. Schweizerische Medizinische Wochenschrift, 124(44): 1933-1937.

Srinivasan, K., Ramarao, P. 2007. Animal models in type 2 diabetes research: An overview.Indian Journal of Medical Research. 125: 451-472.

Taskinen MR, Nikkila EA. 1979. Lipoprotein lipase activity of adipose tissue and skeletal muscle in insulin-deficient human diabetes. Diabetologia, 17(6): 351-356.

Ventura-Sobrevilla J, Boone-Villa VD, Aguilar CN, Román-Ramos R, Vega-Avila E, Campos-Sepulveda E, Alarcon-Aguilar F. 2011. Effect of varying dose and administration of streptozotocin on blood sugar in male CD1 mice. Proceedings of the Western Pharmacology Society, 54: 5-9.

Wagner, J.D., Kavanagh, K., Ward, G.M., Auerbach, B.J. et al. 2006. Old world nonhuman primates models of type 2 diabetes mellitus. ILAR Journal, 47(3): 259-71.

Wei LL, Lu YR, He SR, Jin X, Zeng L, Zhang S, Chen YN, Tian B, Mai G, Yang G, Zhang J, Wang L, Li HX, Markmann JF, Cheng JQ, Deng SP. 2011. Induction of diabetes with signs of autoimmunity in primates by the injection of multiple-low-dose streptozotocin. Biochemical and Biophysical Research Communications, 412(2): 373-378.

Weiss RB. 1982. Streptozotocin: a review of its pharmacology, efficacy, and toxicity. Cancer Treatment Report, 66(3): 427-438.

Wu D, Zou C, Yue F, Li X, Li S, Zhang YA. 2009. The effect of long-term streptozotocin-induced diabetes mellitus (STZ-DM) on cynomolgus (Macaca fascicularis) monkeys. Journal of Medical Primatology, 38(1): 15-22.

Xian S, Huang S, Su JJ, Qin YF, Ou C, Luo ZJ, Wei MY. 2000. A study on experimental diabetes animal models in tree shrews induced by streptozotocin. Journal of Guangxi Medical University, 17(6): 945-949. [冼苏, 黄松, 苏建家, 秦映芬, 欧超, 罗佐杰, 韦敏怡. 2000. 链脲佐菌素诱导树鼩糖尿病动物模型研究. 广西医科大学学报, 17(6): 945-949.]

Yang SH, Dou KF, Song WJ. 2010. Prevalence of diabetes among men and women in China. New England Journal of Medicine, 362(25): 2425-2426.

Zafar M, Naqvi N, Ahmed M, Kaimkhani ZA. 2009. Altered kidney morphology and enzymes in streptozotocin induced diabetic rats. International Journal of Morphology, 27(3): 783-790.