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 Vmax and Km to fall, but caused Km to rise in erythrocytes from 13 out of 38 diabetic subjects, whose native Km was low (P = 0.0013 compared with control). Vmax and serum triacylglycerol levels were related in normal controls (rs = 0.54, P = 0.038) and in diabetic subjects whose Km fell after N-ethylmaleimide (n = 25, rs = 0.62, P = 0.001). Where the Km rose after N-ethylmaleimide, Vmax and triacylglycerol levels were not related (n = 13, rs = -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.
Abnormal thiol group modulation of sodium– lithium countertransport and membrane fluidity is associated with a disturbed relationship between serum triacylglycerols and membrane function in Type II diabetes
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P. A. SENIOR, T. H. THOMAS, S. M. MARSHALL; Abnormal thiol group modulation of sodium– lithium countertransport and membrane fluidity is associated with a disturbed relationship between serum triacylglycerols and membrane function in Type II diabetes. Clin Sci (Lond) 1 June 2000; 98 (6): 673–680. doi: https://doi.org/10.1042/cs0980673
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