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Exp Clin Endocrinol Diabetes 2009; 117(1): 15-20
DOI: 10.1055/s-2008-1073128
Article

© Georg Thieme Verlag KG Stuttgart · New York

Increased Aldosterone Levels in a Model of Type 2 Diabetes Mellitus

S. Fredersdorf 1 [*] , D. H. Endemann 1 [*] , A. Luchner 1 , D. Heitzmann 1 , C. Ulucan 1 , C. Birner 1 , P. Schmid 1 , B. Stoelcker 1 , M. Resch 1 , F. Muders 1 , G. AJ Riegger 1 , J. Weil 1 , 2
  • 1Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany
  • 2Medizinische Klinik II, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
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Publication History

received 09.12.2007 first decision 28.12.2007

accepted 19.03.2008

Publication Date:
25 August 2008 (online)

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Abstract

Background: Aldosterone is an important mediator of cardiovascular and renal remodeling. Type II diabetes mellitus leads to renal and cardiac end organ damage. We investigated the renin-angiotensin-aldosterone system in a model of type 2 diabetes mellitus with known diabetic nephropathy and cardiac remodeling, the Zucker Diabetic Fatty rat with and without ACE-inhibition (ZDF and ZDF+ACE-I) and its control, the Zucker Lean (ZDL) rat.

Methods: Male animals were studied from an age of 7–24 weeks. At ages 7, 14, 17, 20, and 23 weeks, urinary excretion of aldosterone-glucuronide and potassium was assessed. ACE-inhibition with ramipril was started orally at week 13 (1 mg/kg/d). At the end of the study rats were sacrificed and plasma aldosterone concentration and plasma renin activity were measured. Aldosterone synthase (CYP11B2) mRNA expression in the adrenals, kidney, heart and adipose tissue was assessed by real-time PCR. Urinary albumin excretion as marker for diabetic nephropathy was measured in metabolic cages and correlated to aldosterone.

Results: Plasma aldosterone concentration and aldosterone-glucuronide was significantly elevated in ZDF rats, and significantly reduced by ACE-inhibiton. In contrast, plasma renin activity was significantly reduced in ZDF rats and normalized by ACE-inhibition. The urinary aldosterone correlated significantly to albuminuria. Adrenal CYP11B2 expression was not significantly higher in ZDF rats. CYP11B2 mRNA was not detected in the kidney, heart and adipose tissue.

Conclusion: In ZDF rats, urinary and plasma aldosterone levels were elevated despite reduced plasma renin activity. The reversible effect of ACE-inhibition shows that the up-regulation of aldosterone must be dependent of the renin-angiotensin-system in this type II diabetes model. The correlation between aldosterone and diabetic nephropathy suggests a clinical relevance of this observation.

Key words

aldosterone - diabetes type 2 - rat

References

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1 Both authors contributed equally

Correspondence

S. FredersdorfMD 

Klinik und Poliklinik für Innere Medizin II

Franz-Josef-Strauss-Allee 11

University of Regensburg

93042 Regensburg

Germany

Phone: +49/941/944 72 10

Fax: +49/941/944 73 39

Email: sabine.fredersdorf@klinik.uni-regensburg.de

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