Modified streptozotocin-induced diabetic model in rodents

Abstract

Streptozotocin (STZ)-induced type I diabetes mellitus (DM) models have been pivotal in diabetes research due to their ability to mimic the insulin-dependent hyperglycemia akin to human type I diabetes. However, these models often suffer from poor induction rates and low survival post-STZ induction, especially in long-term experiments, necessitating insulin supplementation, which introduces additional variables to experiments. To address this, we present a novel modification to the STZ-induced DM model in C57BL/6J mice to improve survival rates without insulin supplementation. Our method involves non-fasting, low-dose STZ injections dissolved in pH-neutral phosphate buffer saline instead of acidic sodium citrate buffer, administered over 5 days. We observed hyperglycemia induction in 94.28% of mice within a week post-injection, with stable high blood glucose levels, stable body weight, and minimal mortality up to 21 weeks. Notably, omitting 10% sucrose in water and fasting did not affect hyperglycemia induction. Our findings suggest that the modified protocol not only decreases the experimental effort of the researchers, but reduces animal stress and mortality, thus enhancing experimental outcomes and animal welfare. By optimizing the STZ-induced DM model in C57BL/6J mice, our study provides a valuable resource for researchers aiming to study diabetes and its complications while minimizing experimental variability and animal usage.

Keywords

hyperglycemia / non-fasting / streptozotocin / Type 1 diabetes mellitus

References

[1] Junod A, Lambert AE, Orci L, Pictet R, Gonet AE, Renold AE. Studies of the diabetogenic action of streptozotocin. Proc Soc Exp Biol Med. 1967;126(1):201-205.

[2] Elias D, Prigozin H, Polak N, Rapoport M, Lohse AW, Cohen IR. Autoimmune diabetes induced by the beta-cell toxin STZ. Immunity to the 60-kDa heat shock protein and to insulin. Diabetes. 1994;43(8):992-998.

[3] Kolb H. Mouse models of insulin dependent diabetes: low-dose streptozocin-induced diabetes and nonobese diabetic (NOD) mice. Diabetes Metab Rev. 1987;3(3):751-778.

[4] Furman BL. Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol. 2015;70:5.47.1-5.47.20.

[5] Chaudhry ZZ, Morris DL, Moss DR, et al. Streptozotocin is equally diabetogenic whether administered to fed or fasted mice. Lab Anim. 2013;47(4):257-265.

[6] Leguina-Ruzzi A, Ortiz R, Velarde V. The streptozotocin-high fat diet induced diabetic mouse model exhibits severe skin damage and alterations in local lipid mediators. Biom J. 2018;41(5):328-332.

[7] Furman BL. Streptozotocin-induced diabetic models in mice and rats. Curr Protoc. 2021;1(4):e78.

[8] Paik SG, Fleischer N, Shin SI. Insulin-dependent diabetes mellitus induced by subdiabetogenic doses of streptozotocin: obligatory role of cell-mediated autoimmune processes. Proc Natl Acad Sci USA. 1980;77(10):6129-6133.

[9] Akinlade OM, Owoyele BV, Soladoye AO. Streptozotocin-induced type 1 and 2 diabetes in rodents: a model for studying diabetic cardiac autonomic neuropathy. Afr Health Sci. 2021;21(2):719-727.

[10] Gvazava IG, Kosykh AV, Rogovaya OS, et al. A simplified streptozotocin-induced diabetes model in nude mice. Acta Nat. 2020;12(4):98-104.

[11] Wu J, Yan LJ. Streptozotocin-induced type 1 diabetes in rodents as a model for studying mitochondrial mechanisms of diabetic β cell glucotoxicity. Diabetes Metab Syndr Obes. 2015;8:181-188.

[12] Nørgaard SA, Sand FW, Sørensen DB, Abelson KS, Søndergaard H. Softened food reduces weight loss in the streptozotocin-induced male mouse model of diabetic nephropathy. Lab Anim. 2018;52(4):373-383.

[13] Morley LA, Gomez TH, Goldman JL, Flores R, Robinson MA. Accuracy of 5 point-of-care glucometers in C57BL/6J mice. J Am Assoc Lab Anim Sci. 2018;57(1):44-50.

[14] Turner PV, Pekow C, Vasbinder MA, Brabb T. Administration of substances to laboratory animals: equipment considerations, vehicle selection, and solute preparation. J Am Assoc Lab Anim Sci. 2011;50(5):614-627.

[15] Deeds MC, Anderson JM, Armstrong AS, et al. Single dose streptozotocin-induced diabetes: considerations for study design in islet transplantation models. Lab Anim. 2011;45(3):131-140.

RIGHTS & PERMISSIONS

2024 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.