AI Article Synopsis
- Rats fed a high fat diet and given a low dose of streptozotocin (STZ) developed type 2 diabetes characterized by insulin resistance, elevated insulin levels, and kidney damage, which was more severe than in type 1 diabetes models.
- Despite exhibiting lower blood glucose levels compared to type 1 diabetes rats, the type 2 diabetes group showed higher blood pressure and significant urinary protein excretion, indicating kidney function issues.
- The study highlights a new non-genetic rat model for type 2 diabetes and nephropathy, demonstrating important differences in kidney damage and disease progression between type 1 and type 2 diabetes.
Article Abstract
Background: Rats fed a high fat diet and given a low dose of streptozotocin (STZ) (35 mg/kg) develop type 2 diabetes with insulin resistance, hyperinsulinemia, moderate hyperglycemia, hyperlipidemia, and salt-sensitive hypertension. We postulated that rats with noninsulinopenic (type 2) diabetes develop lesions of diabetic nephropathy significantly more prominent than those seen in classic insulinopenic (type 1) diabetic rats.
Methods: Rats were fed regular chow or high fat diet (60% calories from fat and 70% animal fat). After 5 weeks, rats fed regular chow received vehicle (controls) or 55 mg/kg STZ (type 1 diabetes mellitus). Rats fed high fat diet received vehicle (high fat) or low dose STZ, 35 mg/kg (type 2 diabetes mellitus). Rats were sacrificed 14 weeks after STZ/vehicle injection.
Results: Blood glucose, systolic blood pressure, and urinary protein excretion were significantly higher in both diabetes groups than in controls. Serum insulin levels (ng/mL) were higher in type 2 diabetes than in type 1 diabetes groups (0.49 +/- 0.12 vs. 0.07 +/- 0.07) (P= 0.01). Percentage of sclerosed glomeruli was significantly higher in type 2 diabetes group than in control and type 1 diabetes groups. Fibronectin expression was significantly increased in high fat, type 1 and type 2 diabetes groups compared to controls. The expression of type IV collagen, connective tissue growth factor (CTGF), and transforming growth factor-beta (TGF-beta) was significantly increased in high fat and type 2 diabetes groups compared to controls.
Conclusion: Rats fed a high fat diet and given a low dose of STZ developed diabetes (with normal/high insulin levels), hypertension, and proteinuria. Kidney lesions in this type 2 model appear to be more pronounced than in type 1 diabetic rats despite lower blood glucose levels and proteinuria. We present a nongenetic rat model of type 2 diabetes mellitus and nephropathy.
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| http://dx.doi.org/10.1111/j.1523-1755.2005.00727.x | DOI Listing |
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