Altered Renal Sodium Transporter Expression in an Animal Model of Type 2 Diabetes Mellitus.
10.3346/jkms.2007.22.6.1034
- Author:
Yun Kyu OH
1
;
Kwon Wook JOO
;
Jay Wook LEE
;
Un Sil JEON
;
Chun Soo LIM
;
Jin Suk HAN
;
Mark A KNEPPER
;
Ki Young NA
Author Information
1. Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Diabetic Nephropathies;
Rats, Inbred OLETF;
Sodium-Hydrogen Exchanger 3;
Bumetanide Sensitive NaK2Cl Cotransporter;
Thiazide Sensitive Nacl Cotransporter;
Epithelial Sodium Channel
- MeSH:
Animals;
Blood Glucose/analysis;
Diabetes Mellitus, Type 2/*metabolism;
*Disease Models, Animal;
Epithelial Sodium Channel/*analysis;
Hypertension/complications;
Immunoblotting;
Immunohistochemistry;
Kidney/*metabolism;
Male;
Rats;
Sodium/*metabolism;
Sodium-Hydrogen Antiporter/genetics;
Sodium-Potassium-Chloride Symporters/genetics
- From:Journal of Korean Medical Science
2007;22(6):1034-1041
- CountryRepublic of Korea
- Language:English
-
Abstract:
Hemodynamic factors play an important role in the development and/or progression of diabetic nephropathy. We hypothesized that renal sodium transporter dysregulation might contribute to the hemodynamic alterations in diabetic nephropathy. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as an animal model for type 2 diabetes. Long Evans Tokushima (LETO) rats were used as controls. Renal sodium transporter regulation was investigated by semiquantitative immunoblotting and immunohistochemistry of the kidneys of 40-week-old animals. The mean serum glucose level in OLETF rats was increased to 235+/-25 mg/dL at 25 weeks, and the hyperglycemia continued up to the end of 40 weeks. Urine protein/ creatinine ratios were 10 times higher in OLETF rats than in LETO rats. At 40th week, the abundance of the epithelial sodium channel (ENaC) beta-subunit was increased in OLETF rats, but the abundance of the ENaC gamma-subunit was decreased. No significant differences were observed in the ENaC alpha-subunit or other major sodium transporters. Immunohistochemistry for the ENaC beta-subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC gamma-subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC beta-subunit upregulation and ENaC gamma-subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance.
