Circulating alpha-klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathy

Cardiovascular Diabetology

Original Investigation

Hans-Peter Hammes¹  Bruce H R Wolffenbuttel²  Marc G Vervloet³  Jan-Luuk Hillebrands⁴  Joris van Ark⁴  Harry van Goor⁴  Marcory C R F van Dijk⁵ 

[1] 5th Medical Department, Section of Endocrinology, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany;Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands;Department of Pathology & Medical Biology, Pathology, University of Groningen, University Medical Center Groningen, P.O. Box 30, Hanzeplein 1, 001, Groningen, The Netherlands;Department of Pathology & Medical Biology, Pathology, University of Groningen, University Medical Center Groningen, P.O. Box 30, Hanzeplein 1, 001, Groningen, The Netherlands;Department of Pathology, Rijnstate Hospital, Arnhem, The Netherlands;

关键词: Atherosclerosis;    Coronary artery disease;    Klotho;    Macrovascular disease;    Peripheral artery disease;    Type 2 diabetes;   

DOI  :  10.1186/1475-2840-12-116

 received in 2013-05-22, accepted in 2013-08-12,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundDiabetes is associated with a high incidence of macrovascular disease (MVD), including peripheral and coronary artery disease. Circulating soluble-Klotho (sKlotho) is produced in the kidney and is a putative anti-aging and vasculoprotective hormone. Reduced Klotho levels may therefore increase cardiovascular risk in diabetes. We investigated if sKlotho levels are decreased in type 2 diabetes and associate with MVD in the absence of diabetic nephropathy, and whether hyperglycemia affects renal Klotho production in vitro and in vivo.MethodssKlotho levels were determined with ELISA in diabetic and non-diabetic patients with and without MVD, and healthy control subjects. Human renal tubular epithelial cells (TECs) were isolated and exposed to high glucose levels (15 and 30 mM) in vitro and Klotho levels were measured with qPCR and quantitative immunofluorescence. Klotho mRNA expression was quantified in kidneys obtained from long term (3 and 8 months) diabetic Ins2Akita mice and normoglycemic control mice.ResultsNo significant differences in sKlotho levels were observed between diabetic patients with and without MVD (527 (433–704) pg/mL, n = 35), non-diabetic MVD patients (517 (349–571) pg/mL, n = 27), and healthy control subjects (435 (346–663) pg/mL, n = 15). High glucose (15 and 30 mM) did not alter Klotho expression in TECs. Long-term hyperglycemia in diabetic Ins2Akita mice (characterized by increased HbA1c levels [12.9 ± 0.3% (3 months) and 11.3 ± 2.0% (8 months)], p < 0.05 vs. non-diabetic mice) did not affect renal Klotho mRNA expression.ConclusionsThese data indicate that sKlotho levels are not affected in type 2 diabetes patients with and without MVD. Furthermore, hyperglycemia per se does not affect renal Klotho production. As type 2 diabetes does not alter sKlotho levels, sKlotho does not seem to play a major role in the pathogenesis of MVD in type 2 diabetes.

【 授权许可】

Unknown   
© van Ark et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.