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
Pa. Senior et al., 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, 98(6), 2000, pp. 673-680
In essential hypertension and diabetic nephropathy, sodium-lithium countert
ransport (Na-Li CT) is an inherited marker, subject to metabolic influences
, of cardiovascular risk. Studies in Type II diabetes, taking clinical phen
otypes as their starting point, are conflicting. We sought to identify Na-L
i CT kinetic abnormalities in Type II diabetes, and only subsequently to se
ek relationships with clinical variables. Na-Li CT kinetics, membrane fluid
ity and their modulation by thiol proteins were measured in erythrocytes fr
om 38 patients with Type II diabetes and in 16 normal control subjects. In
untreated erythrocytes, Na-Li CT kinetics were similar. Thiol protein alkyl
ation with N-ethylmaleimide generally caused both V-max and K-m to fall, bu
t caused K-m to rise in erythrocytes from 13 out of 38 diabetic subjects, w
hose 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 = 2
5, r(s) = 0.62, P = 0.001). Where the K-m rose after N-ethylmaleimide, V-ma
x 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, albumi
nuria, glycaemia or lipid profiles. Thus abnormalities in the regulation of
Na-Li CT and membrane fluidity by key thiol proteins, resembling those see
n in essential hypertension and diabetic nephropathy, were apparent in one-
third of subjects with Type II diabetes. Membrane abnormalities may indicat
e a common pathological mechanism. The prognostic significance of Na-Li CT
kinetic abnormalities in Type II diabetes must now be confirmed.