eprintid: 21773
rev_number: 11
eprint_status: archive
userid: 1589
dir: disk0/00/02/17/73
datestamp: 2016-08-18 13:06:09
lastmod: 2024-05-07 18:33:23
status_changed: 2016-08-18 13:06:09
type: article
metadata_visibility: show
creators_name: van Ark, Joris
creators_name: Hammes, Hans-Peter
creators_name: van Dijk, Marcory C. R. F.
creators_name: Vervloet, Marc G.
creators_name: Wolffenbuttel, Bruce H. R.
creators_name: van Goor, Harry
creators_name: Hillebrands, Jan-Luuk
title: Circulating alpha-klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathy
subjects: ddc-610
divisions: i-61400
abstract: Background: Diabetes 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.   Methods: sKlotho 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.   Results: No 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.   Conclusions: These 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.
date: 2013
publisher: BioMed Central
id_scheme: DOI
ppn_swb: 1658538900
own_urn: urn:nbn:de:bsz:16-heidok-217735
language: eng
bibsort: VANARKJORICIRCULATIN2013
full_text_status: public
publication: Cardiovascular Diabetology
volume: 12
number: 116
place_of_pub: London
pagerange: 1-10
issn: 1475-2840
citation:   van Ark, Joris ; Hammes, Hans-Peter ; van Dijk, Marcory C. R. F. ; Vervloet, Marc G. ; Wolffenbuttel, Bruce H. R. ; van Goor, Harry ; Hillebrands, Jan-Luuk  (2013) 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, 12 (116).  pp. 1-10.  ISSN 1475-2840     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/21773/1/12933_2013_Article_704.pdf