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Lookup NU author(s): Dr Peter Senior,
Dr Trevor Thomas,
Emerita Professor Sally Marshall
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In essential hypertension and diabetic nephropathy, sodium-lithium countertransport (Na-Li CT) is an inherited marker, subject to metabolic influences, of cardiovascular risk. Studies in Type II diabetes, taking clinical phenotypes as their starting point, are conflicting. We sought to identify Na-Li CT kinetic abnormalities in Type II diabetes, and only subsequently to seek relationships with clinical variables. Na-Li CT kinetics, membrane fluidity and their modulation by thiol proteins were measured in erythrocytes from 38 patients with Type II diabetes and in 16 normal control subjects. In untreated erythrocytes, Na-Li CT kinetics were similar. Thiol protein alkylation with N-ethylmaleimide generally caused both V(max) and K(m) to fall, but caused K(m) to rise in erythrocytes from 13 out of 38 diabetic subjects, whose native K(m) was low (P = 0.0013 compared with control). V(max) and serum triacylglycerol levels were related in normal controls (r(s) = 0.54, P = 0.038) and in diabetic subjects whose K(m) fell after N-ethylmaleimide (n = 25, r(s) = 0.62, P = 0.001). Where the K(m) rose after N-ethylmaleimide, V(max) and triacylglycerol levels were not related (n = 13, r(s) = -0.39, P = 0.183) and membrane fluidity did not increase after N-ethylmaleimide. However, these subgroups were indistinguishable in terms of blood pressure, albuminuria, glycaemia or lipid profiles. Thus abnormalities in the regulation of Na-Li CT and membrane fluidity by key thiol proteins, resembling those seen in essential hypertension and diabetic nephropathy, were apparent in one-third of subjects with Type II diabetes. Membrane abnormalities may indicate a common pathological mechanism. The prognostic significance of Na-Li CT kinetic abnormalities in Type II diabetes must now be confirmed.
Author(s): Marshall SM; Senior PA; Thomas TH
Publication type: Article
Publication status: Published
Journal: Clinical Science
ISSN (print): 0143-5221
ISSN (electronic): 1470-8736
Publisher: Portland Press
PubMed id: 10814604