Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia, which is divided into type 1 (T1DM), type 2 (T2DM) and other special types. The following are the construction methods and key points of commonly used experimental models.
principle : Destroy pancreatic β cells through chemical drugs or immunity to simulate absolute insulin deficiency.
Common methods :
|
method |
Procedure |
Features |
|
Streptozotocin (STZ)-induced |
- Mouse : Single intraperitoneal injection of STZ (50-200 mg/kg, dissolved in citrate buffer, pH 4.5). |
Low cost and high success rate (>80%). Blood sugar must be monitored ≥16.7 mmol/L for 3 consecutive days to confirm success. |
|
Alloxan-induced |
Single intraperitoneal injection (mice: 50-100 mg/kg; rats: 100-200 mg/kg) |
It has lower selectivity for β cells than STZ and is more likely to cause liver and kidney damage. |
|
NOD mice (spontaneous model) |
Nonobese diabetic (NOD) mice spontaneously develop autoimmune insulitis after 8-12 weeks of age. |
It simulates the natural course of human T1DM, but the modeling period is long (3-6 months). |
|
method |
Procedure |
Features |
|
HFD+STZ combined induction |
- 4-8 weeks of high-fat diet (60% fat for energy) to induce insulin resistance. |
Simulate the pathological process of T2DM "insulin resistance → β-cell failure", with a modeling rate of >70%. |
|
db/db mice (Lepr deficient) |
B6.BKS(D)-Leprdb/J mice, which suffer from obesity, hyperglycemia and insulin resistance due to leptin receptor mutation. |
No induction is required, and hyperglycemia occurs at 4 weeks of age, making it suitable for studying obesity-related T2DM. |
|
ZDF rats (Zucker Diabetic Fatty) |
Carrying Lepr mutation, mice fed a high-fat diet develop severe insulin resistance and β-cell apoptosis. |
Stable simulation of late complications of human T2DM (such as kidney disease). |
method : Pregnant mice were injected with STZ (35-50 mg/kg) in the second trimester of pregnancy (mice: GD10-12; rats: GD6-8) to destroy the compensatory capacity of β cells.
Evaluation indicators ：Fasting blood glucose during pregnancy ≥7.0 mmol/L, blood glucose recovered after delivery.
blood sugar ：Fasting blood glucose ≥7.0 mmol/L (diabetes diagnostic standard), dynamic monitoring of oral glucose tolerance (OGTT) and insulin tolerance (ITT).
Insulin levels : Serum insulin was detected by ELISA and HOMA-IR (insulin resistance index) was calculated.
Blood lipids ：Detect total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL).
Islet morphology ：HE staining was used to observe the size of pancreatic islets and the number of β cells; immunohistochemistry was used to detect the expression of insulin (INS) and glucagon (Glucagon).
β-cell apoptosis : TUNEL staining was used to quantify the proportion of apoptotic cells.
Diabetic nephropathy ：Urine microalbumin (UACR), glomerular basement membrane thickening (PAS staining).
Diabetic retinopathy : Fundus imaging was used to observe microaneurysms, and ERG was used to detect retinal function.
Peripheral neuropathy : Hot plate test (pain sensitivity), nerve conduction velocity measurement.
|
Model Type |
advantage |
limitation |
|
STZ-induced T1DM |
Low cost, simple operation, short molding cycle (1-2 weeks) |
Individual differences are large, and strict temperature control is required (STX is sensitive to temperature) |
|
db/db mice |
Spontaneous T2DM, stable phenotype, suitable for long-term research |
Expensive (≈$100/bird), requires dedicated breeding facilities |
|
HFD+STZ combined induction |
Simulates the natural progression of human T2DM and can regulate the severity of modeling |
High-fat diet can easily cause hepatic steatosis and interfere with experimental results |
Drug Screening : Testing insulin sensitizers (such as metformin), GLP-1 receptor agonists, or SGLT2 inhibitors.
Mechanism of complications ：Study hyperglycemia-induced oxidative stress and inflammatory signals (NF-κB, NLRP3).
Gene therapy ：The repair effect of CRISPR/Cas9 editing diabetes-related genes (such as GCK and INS).
Intestinal flora research ：Fecal microbiota transplantation (FMT) explores the impact of the microbiota-metabolism axis on diabetes.
STZ toxicity control :
Provide 10% glucose solution within 48 hours after injection to prevent hypoglycemic shock.
Avoid repeated freezing and thawing of STZ solution (it must be prepared and used immediately).
Diet control : Food intake and body weight changes must be strictly recorded during HFD induction.
Code of Ethics :
Blood sugar >33.3 mmol/L or body weight loss >20% requires immediate intervention or euthanasia.
Pain management: Use ibuprofen or local anesthesia (eg, plantar irritation test).
|
Group |
Fasting blood glucose (mmol/L) |
Insulin (ng/mL) |
Urine albumin (μg/24h) |
|
Control group |
5.2 ± 0.6 |
0.8 ± 0.2 |
10 ± 3 |
|
STZ-induced T1DM group |
25.1 ± 3.4 |
0.2 ± 0.1 |
15 ± 4 |
|
db/db mouse group |
18.6 ± 2.8 |
5.5 ± 1.2 |
120 ± 25 |
