Nephrology Dialysis Transplantation, Vol 12, Issue 7 1336-1343, Copyright © 1997 by Oxford University Press
A Kramer-Guth, T Quaschning, H Pavenstadt, J Galle, M Nauck, MW Baumstark, P Schollmeyer, W Marz and C Wanner
BACKGROUND: Recent studies suggest that dyslipidaemia accelerates the
progression of diabetic nephropathy, but the various pathomechanisms
underlying such abnormalities are not completely delineated. METHODS: We
isolated, radiolabelled, and characterized very-low-density lipoproteins
(VLDL) and low-density lipoproteins (LDL) from eight diabetic patients with
moderate impairment of renal function and dyslipidaemia and studied their
interaction with LDL receptors in human glomerular epithelial cells.
RESULTS: While diabetic VLDL showed no compositional changes, LDL particles
contained a higher proportion of triglycerides at the expense of
cholesterol in comparison with healthy controls. Despite differences in
composition, both VLDL and LDL from patients exhibited reduced receptor
affinity and cellular uptake capacity by glomerular epithelial cells. Since
LDL composition was altered intracellular cholesterol homeostasis was
investigated. Due to reduced cholesterol content and lower uptake capacity,
diabetic LDL were less effective in suppressing intracellular sterol
synthesis and in activating acylcholesterol acyltransferase than LDL from
controls. Electrophoretic mobility of apoB from diabetic patients was
enhanced as compared to controls, most probably due to the higher degree of
glycation (17 + 1.7 versus 11 + 1%, P < 0.05) but not to oxidation
(TBARS 0.5 + 0.2 versus 0.2 + 0.1 mumol/1). Oxidized LDL was not taken up
in significant amounts, indicating no scavenger receptor activity in
glomerular epithelial cells. CONCLUSION: The receptor-specific uptake of
diabetic VLDL and LDL by glomerular epithelial cells is impaired.
Compositional changes of the LDL particle and glycation of the protein
moiety may contribute to altered glomerular uptake. However, glycation of
the protein moiety may be superior to compositional changes. Because
glomerular structures like mesangial matrix and endothelial cells are known
for preferential binding of modified lipoproteins, further studies are
required to elucidate their potential role in the progression of diabetic
glomerulosclerosis.
ORIGINAL ARTICLES
Uptake and metabolism of lipoproteins from patients with diabetes mellitus type II by glomerular epithelial cells
Department of Medicine, University of Freiburg, Germany.
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  T. QUASCHNING, M. SCHÖMIG, M. KELLER, J. THIERY, M. NAUCK, P. SCHOLLMEYER, C. WANNER, and A. KRÄMER-GUTH Non-Insulin-Dependent Diabetes Mellitus and Hypertriglyceridemia Impair Lipoprotein Metabolism in Chronic Hemodialysis Patients J. Am. Soc. Nephrol., February 1, 1999; 10(2): 332 - 341. [Abstract] [Full Text]
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