Streptozotocin-Induced Diabetes in a Mouse Model (BALB/c) Is Not an Effective Model for Research on Transplantation Procedures in the Treatment of Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is characterized by the destruction of over 90% of the β-cells. C-peptide is a parameter for evaluating T1D. Streptozotocin (STZ) is a standard method of inducing diabetes in animals. Eight protocols describe the administration of STZ in mice; C-peptide levels are not taken into account. The aim of the study is to determine whether the STZ protocol for the induction of beta-cell mass destruction allows for the development of a stable in vivo mouse model for research into new transplant procedures in the treatment of type 1 diabetes. Materials and methods: Forty BALB/c mice were used. The animals were divided into nine groups according to the STZ dose and a control group. The STZ doses were between 140 and 400 mg/kg of body weight. C-peptide was taken before and 2, 7, 9, 12, 14, and 21 days after STZ. Immunohistochemistry was performed. The area of the islet and insulin-/glucagon-expressing tissues was calculated. Results: Mice who received 140, 160, 2 × 100, 200, and 250 mg of STZ did not show changes in mean fasting C-peptide in comparison to the control group and to day 0. All animals with doses of 300 and 400 mg of STZ died during the experiment. The area of the islets did not show any differences between the control and STZ-treated mice in groups below 300 mg. The reduction of insulin-positive areas in STZ mice did not exceed 50%. Conclusions: Streptozotocin is not an appropriate method of inducing a diabetes model for further research on transplantation treatments of type 1 diabetes, having caused the destruction of more than 90% of the β-cell mass in BALB/c mice.

Molecular and morphological alterations in uninjured skin of streptozotocin‐induced diabetic mice

“…In the present study, we found that STZ-induced diabetes resulted in a significant increase in blood glucose, as mice developed severe hyperglycemia with concentrations reaching 400 mg/dL. Repeated administration of five low doses of STZ resulted in cellular and humoral immune reactions against β cells following subsequent infiltration of macrophages and lymphocytes, leading to β-cell lysis and type 1 diabetes ( 9 ). Despite the hyperglycemia, mice with STZ-induced diabetes did not become insulin-resistant.…”

“…Therefore, we used streptozotocin (STZ)-induced diabetic mice. STZ is an antibiotic that promotes complete or partial destruction of pancreatic β cells and is commonly used experimentally to produce a type 1 diabetic animal model ( 9 ). We divided C57BL/6 mice into two groups, diabetic and non-diabetic, and we performed hematoxylin/eosin, picrosirius red, and Nissl staining.…”

Effects of Piper sarmentosum Roxb. on hypertension and diabetes mellitus: A systematic review and meta-analysis

“…Alloxan and STZ are the most popular diabetogenic chemicals in diabetes research. However, STZ has notable advantages over alloxan due to its rapid onset, the long half-life, low toxicity and cost-effectiveness ( Wszola et al, 2021 ). STZ is a toxic glucose analogue that is preferentially accumulated in the pancreatic β-cells via the GLUT2 glucose transporters in the plasma membrane.…”

“…Additionally, GLUT2 transporters are not only expressed in pancreatic β-cells, but also in the epithelial cells of the kidneys and hepatocytes ( Sędzikowska and Szablewski, 2021 ; Yang et al, 2022 ). Thus, administration of STZ may result in nephro- and hepatotoxicity along with its potential to damage pancreatic β-cells ( Wszola et al, 2021 ). All six animal studies that investigated the effects of PS on diabetes used a single, high dose of STZ injection (up to 75 mg/kg) to induce pancreatic β-cells damage and diabetes in rats, which mimics type 1 diabetes.…”

Guidelines for cellular and animal models of insulin resistance in type 2 diabetes

“…Obviously, the dose of STZ is the key factor and a large injection dose will completely damage the islets. And absolute lack of insulin will result in type 1 diabetes (Wszola et al, 2021). Before STZ injection, rats and mice need to fast for 12 h without water, and males are used as much as possible because the response of females to STZ is not uniform, which may be related to estrogen levels.…”