Kidney involvement in a nongenetic rat model of type 2 diabetes.
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.


CONCLUSIONS
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.
Danda
Ratna S
RS
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229-3900, USA.
Habiba
Nusrath M
NM
Rincon-Choles
Hernan
H
Bhandari
Basant K
BK
Barnes
Jeffrey L
JL
Abboud
Hanna E
HE
Pergola
Pablo E
PE
D000818:Animals; D001786:Blood Glucose; D001794:Blood Pressure; D001835:Body Weight; D024141:Collagen Type IV / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000378:metabolism; D007328:Insulin / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D009929:Organ Size; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism
D001786:Blood Glucose; D024141:Collagen Type IV; D055513:Connective Tissue Growth Factor; D005353:Fibronectins; D006442:Glycated Hemoglobin; D017874:Immediate-Early Proteins; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; D016212:Transforming Growth Factor beta; C526316:CCN2 protein, rat