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.
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.
Senior
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Human Diabetes and Metabolism Research Centre, University of Newcastle upon Tyne, Newcastle, U.K. p.senior@free4all.co.uk
Thomas
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Marshall
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D000328:Adult; D000368:Aged; D017920:Antiporters / Q000097:blood* / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D004910:Erythrocyte Membrane / Q000502:physiology; D005033:Ethylmaleimide / Q000494:pharmacology; D006801:Humans; D008094:Lithium / Q000097:blood; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D012964:Sodium / Q000097:blood; D013438:Sulfhydryl Compounds / Q000502:physiology*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood*
D017920:Antiporters; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D014280:Triglycerides; C045885:sodium-lithium countertransporter; D008094:Lithium; D012964:Sodium; D005033:Ethylmaleimide