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Increased urinary excretion of angiotensinogen(AGT) in type II diabetic mice
Author(s) -
Belmadani Souad,
Park S,
Bivona B J,
Seth D,
Kobori H,
HarrisonBernard L M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.944.4
Subject(s) - endocrinology , medicine , excretion , diabetic nephropathy , polyuria , glomerulosclerosis , proteinuria , diabetes mellitus , renin–angiotensin system , angiotensin ii , kidney , nephropathy , kidney disease , focal segmental glomerulosclerosis , chemistry , blood pressure
Diabetic nephropathy is the leading cause of end‐stage renal disease in the Western world leading to increased morbidity and mortality in type II diabetic patients. The renin‐angiotensin system (RAS) remains the major therapeutic target to slow the progression of renal disease in diabetes. The db/db mouse develops significant proteinuria, hyperglycemia, glomerulosclerosis, and insulin resistance with abnormalities similar to Type II diabetic nephropathy in humans. Ye et al. (Hypertension, 2004) reported that renal cortical angiotensin converting enzyme (ACE) activity is low, while ACE2 protein expression is high in db/db compared to db/m mice; therefore, studies were performed to test the hypothesis that intrarenal ANG II levels are reduced in db/db mice. Kidney ANG II (1,017±165 vs 788±99 fmol/g) and plasma ANG II levels (247±26 vs 391±105 fmol/ml) were not different between db/db and db/m mice, respectively. Kidney ANG I levels were also similar (113±24 db/db vs 110±45 fmol/g db/m; NS). In contrast, urinary excretion of AGT was significantly elevated in db/db compared to db/m mice (66±16 vs 12±2 ng/d, p<0.001). Urinary excretion of albumin was also increased in db/db mice (1,075±170 vs 125±8; p<0.001). Interestingly, excretion of AGT and albumin were positively correlated (R2=0.8). Polydipsia (7.8±1.1 vs 3.1±0.4 ml/d; p<0.001), polyuria (5.1±0.9 vs 1.1±0.2; p<0.001), hyperglycemia (408±19 vs 150±6 mg/dl; p<0.001), hyperleptinemia (108.1±26 vs 4.2±0.8 mg/L; p<0.001), and hyperinsulinemia (11.8±3.3 vs 1.3±0.4 mg/L; p<0.001) are clearly evident in 18 wk old male db/db compared to db/m mice, respectively. In summary, urinary excretion of AGT and albumin are positively correlated and may represent a novel marker for the progression of diabetic renal disease.