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

• Published in: Clinical science (1979) Vol. 98; no. 6; pp. 673 - 680
• Main Authors: SENIOR, P. A, THOMAS, T. H, MARSHALL, S. M
• Format: Journal Article
• Language: English
• Published: London Portland Press 01.06.2000
• Subjects: Adult; Aged; Antiporters - blood; Antiporters - drug effects; Associated diseases and complications; Biological and medical sciences; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Erythrocyte Membrane - physiology; Ethylmaleimide - pharmacology; Humans; Lithium - blood; Medical sciences; Membrane Fluidity - drug effects; Membrane Fluidity - physiology; Middle Aged; Sodium - blood; Sulfhydryl Compounds - physiology; Sulfhydryl Reagents - pharmacology; Triglycerides - blood; Endocrinopathy; Kidney disease; Human; Thiol; Urinary system disease; Non insulin dependent diabetes; Protein; Nephropathy; Fluidity; Sodium; Membrane transport; Risk factor; Complication; Membrane
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/CS19990307

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.