Introduction of
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Streptozotocin (Streptozocin; STZ) is an antibiotic widely used in experimental animal models of induced diabetes. Streptozotocin enters B cells via the glucose transporter (GLUT2) and causes the alkylation of DNA ( DNA-methylating ). Streptozotocin can induce the apoptosis of β cells[1][2][3].
IC50 & Target:DNA alkylator[2]
In Vitro:The IC50 values of Streptozotocin for HL60, K562 and C1498 cells were 11.7, 904 and 1024 μg/ml, respectively[3].
Streptozotocin (0-20 mM, 48 h) (dissolved in citrate buffer, pH 4.4 and diluted in DMEM just before use) induces cytotoxicity, oxidative stress and mitochondrial dysfunction in HepG2 cells[7].
Streptozotocin (10 mM, 0-120 min) (dissolved in 50 mM sodium citrate and 0.45% NaCl, pH 4.5) is specifically transported by GLUT2, which contributes to the cytotoxicity in GLUT2-expressing cells[8].
In Vivo:Note:
Please do not refer to only one article to determine the experimental conditions. It is recommended to determine the optimal experimental conditions (animal strain, age, dosage, frequency and cycle, detection time and indicators, etc.) through preliminary experiments before the formal experiment.
Streptozotocin is suitable for constructing models of type 1 and type 2 diabetes. Streptozotocin is highly water-soluble, which is often dissolved in cold acidic citric acid buffer (pH 4.0-4.7), commonly used in animal experiments, ready for use. Once absorbed, distributes widely throughout the body, including crossing the blood-brain barrier and placenta, entering various tissues. In the liver, Streptozotocin undergoes chemical modification, converting into an active form that causes DNA methylation and damages pancreatic β-cells, leading to diabetes. The elimination half-life of Streptozotocin varies depending on the species and route of administration.
Induction of Type 1 Diabetes Mellitus (T1DM)[3][4][5]
Background
Induces disease by direct destroying the animal's islet β beta cells.
Specific Modeling Methods
Mice: C57BL/6 • Male • 8-12 week-old
Administration: 100 mg/kg-220 mg/kg • i.p. • single high dose, or 40-60 mg/kg for five consecutive days.
Rat: Sprague-Dawley or Wistar rats • male • 8-10 weeks-old
Administration: 65 mg/kg • i.p. • single high dose.
Note
Tips:
1) The sensitivity of different species of animals to STZ varies greatly, and it is recommended to use male rats (female mice are more tolerant to STZ) [4];
2) Fasting without water before administration can increase the sensitivity of pancreatic β cells to STZ. STZ injection in model animals generally requires rapid injection;
3) Different strains of mice have different sensitivities to STZ. Studies have reported that the DBA/2 strain is the most sensitive, followed by C57BL6. Balb/cJ mice are resistant to multiple low-dose STZ-induced diabetes[4];
4) After STZ treatment, animals die due to fatal hypoglycemia due to massive necrosis of pancreatic β-cells and sudden release of insulin, usually within 48 hours after injection. To prevent this, it is best to provide animals with 10% sucrose water regularly after STZ treatment. If animal mortality exceeds 20% when using a single high-dose STZ diabetic mouse protocol, treat animals with an intraperitoneal injection of 5% glucose solution within 6 hours of STZ injection[5];
5) preliminary experiments are required, and it is not recommended to directly use the administration methods and dosages in the literature.
Modeling Indicators
Blood glucose level : Random blood glucose levels are generally used as a guide for diabetes. Animals with blood glucose levels above 300 mg/dL (i.e. 16.7 mmol/L) are considered diabetic.
When fasting blood glucose levels are used as an indicator of elevation, values above 150 (8.3 mmoL/L) or 200 mg/dL (11 mmol/L) can be used arbitrarily as a marker of hyperglycemia, depending on the purpose of the study.
Other indicators : generally accompanied by increased water intake, urine volume, and weight loss. Serum biochemical indexes such as total cholesterol, aspartate aminotransferase, triglyceride and low density lipoprotein also increased significantly with the occurrence of diabetes.
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Induction of Type 2 Diabetes Mellitus (T2DM)[3][4][5]
Background
The disease is induced by partially destroying the animals' islet β cells, making the peripheral tissue insensitive to insulin, and by feeding them a high-calorie diet.
Specific Modeling Methods
Mice: C57BL/6 • Male • 10 week-old
Administration: 4-8 weeks of high-fat diet + low-dose i.p. injection of 30-70 mg/kg STZ for 3-5 days or a single i.p. dose of 90- 100 mg/kg.
Rat: Sprague-Dawley or Wistar rats • male • 8-10 weeks-old
Administration: 4-8 weeks of high-fat diet + i.p. injection of 25-40 mg/kg STZ, a single dose.
Note
Tips:
Same precautions as for "Induction of Type 1 Diabetes Mellitus (T1DM)".
Modeling Indicators
Blood glucose level : Blood glucose level exceeds 300 mg/dL(16.7 mmoL/L).
Other indicators : generally accompanied by increased water intake, urine volume, and weight loss. Serum biochemical indexes such as total cholesterol, aspartate aminotransferase, triglyceride and low density lipoprotein also increased significantly with the occurrence of diabetes.
Correlated Product(s): /
Opposite Product(s): /
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