Renin-angiotensin system blockade in correction of glucose metabolic disturbance in uninephrectomized rats
10.3724/SP.J.1008.2015.00761
- Author:
Ke-Ke YANG
1
Author Information
1. Guangxi Key Laboratory of Diabetic System Medicine, Guilin Medical University
- Publication Type:Journal Article
- Keywords:
AMP-activated protein kinase;
Glucose metabolism disorders;
Nephrectomy;
Renal insufficiency;
Renin-angiotensin system
- From:
Academic Journal of Second Military Medical University
2015;36(7):761-766
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate influences of renin-angiotensin system (RAS) blocker on glucose metabolism and expression of AMP-activated protein kinase (AMPK) in renal cortex in uninephrectomized (UNX) rats. Methods A total of 40 rats were divided into four groups, namely, sham, uninephrectomy, UNX rats treated with angiotensin converting enzyme inhibitor (ACEI) Lisinopril and angiotensin receptors blockade (ARB, n=10) Losartan. Rats in the last three groups were made into UNX model reserving single right kidney. Fasting blood samples were collected for measurements of glucose metabolism-related parameters in UNX rats at 3, 6, 8, and 10 months after operation, and renal function-related parameters at 10 months; the expression of AMPK in renal cortex tissues was detected by Western blotting analysis and immunofluorescence in the four groups. Results Compared with the sham rats, UNX rats developed hyperinsulinemia at 3 months after operation, hyperglycemia at 8 months and increased homeostasis model assessment-insulin resistance (HOMA-IR) at 3 and 10 months (P <0.05 for the corresponding parameters). Compared with UNX rats, ACEI and ARB treatments significantly improved hyperinsulinemia, hyperglycemia and HOMA-IR (P <0.05). Compared with the sham rats, UNX rats developed renal dysfunction as reflected by significantly high serum urea (P <0.05), creatinine (P <0.05) and ratio of urinary total protein to creatinine (P <0.05) at 10 months after operation; while these parameters were all significantly decreased in ACEI or ARB rats (P <0.05) compared with UNX rats. Meanwhile, AMPK expression in the renal cortex tissues in UNX rats was the least among the four groups (P <0.01), and those in the ACEI and ARB groups were significantly higher than that in the UNX group (P <0.01). Conclusion RAS blockade may correct glucose metabolic disorders caused by uninephrectomy via restoring AMPK expression, which may serve as a potential therapeutic target for renal dysfunction accompanied with glucose dysmetabolism.
