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

Abstract

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.

Erythrocyte membrane in type 2 diabetes mellitus

“…Insights into the possible pathways underlying could be provided by the significant correlation of increased sodium-lithium countertransport activity with upregulated intracellular sodium concentration and intracellular free calcium-ion concentration described in a study performed on 48 patients with type 2 diabetes and 24 healthy controls 51 . It seems that thiol protein alkylation with N-ethtyl maleimide (NEM) could be one of the mechanisms involved in the impaired regulation of erythrocyte sodium-lithium countertransport and abnormal membrane fluidity in some patients with type 2 diabetes 52,53 (Table 1).…”

Ab Initio, DFT and semi-empirical studies on interactions of phosphoryl, carbonyl, imino and thiocarbonyl ligands with the li+ cation: affinity and associated parameters

“…The most common types of interactions are with oxygen atoms of alcohols, 6 ketones, 7 carboxylic acids 8,9 and phosphates, 10 nitrogen atoms of amines, 9,11 amides 12 and imides 13 and sulfur atoms of thiols. 14 In the biological media the Li + cation is surrounded by different Vol. 23, No.…”