Reduced Na+ -K+ -ATPase Activity and Plasma Lysophosphatidylcholine Concentrations in Diabetic Patients

Abstract

A fraction from normal human plasma inhibiting Na(+)-K(+)-ATPase has been recently identified as lysophosphatidylcholine (LPC). The aim of this study was to investigate the existence of a relationship between the activity of the cellular membrane Na(+)-K(+)-ATPase and plasma LPC in human diabetes. We studied 10 patients with insulin-dependent-diabetes mellitus (IDDM), 14 patients with non-insulin-dependent diabetes mellitus (NIDDM), and 10 sex- and age-matched control subjects. Plasma LPC concentrations were increased in both IDDM and NIDDM patients compared with control subjects. Na(+)-K(+)-ATPase activity was reduced in both groups of patients in erythrocyte and platelet membranes. There was a significant correlation between the concentrations of plasma LPC and Na(+)-K(+)-ATPase activity in both erythrocyte and platelet membranes (P < 0.01). To investigate the effect of LPC on the enzyme, Na(+)-K(+)-ATPase activity was determined in erythrocyte membranes obtained from six healthy subjects after in vitro incubation with increasing concentrations of LPC (1-10 microM). Enzymatic activity was significantly reduced by in vitro LPC at a concentration of 2.5 microM, with a further decrease at 5 microM. These data suggest that the decrease in Na(+)-K(+)-ATPase activity in diabetes might be due to increased LPC concentrations.

Increasing plasma lysophosphatidylcholine levels in patients with regular dextran sulfate lipoprotein apheresis

“…In accordance with our data, the physiological concentration of LPC in plasma has reported to be in the range of 100e170 mM [14,15]. The major fraction of LPC in plasma is bound to albumin and other carrier proteins as well as lipoproteins [16].…”

Group 1B Phospholipase A2–Mediated Lysophospholipid Absorption Directly Contributes to Postprandial Hyperglycemia

“…The results of this study further document that the Pla2g1b-digested product LPC is directly responsible for suppression of hepatic glucose metabolism. In view of studies showing increased LPC levels in patients with type 2 diabetes (27,28), the current study suggests that inhibition of Pla2g1b may be a viable strategy to prevent the onset of type 2 diabetes in individuals consuming a high-glucose/high-fat diet.…”

A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice

“…*P Ͻ 0.05; **P Ͻ 0.01 vs. normal. lin-dependent diabetes mellitus patients (25,30), diabetic retinopathy (15), and experimental obesity (12). Elevated LPC levels cause postprandial hyperglycemia by inhibiting glucose uptake by liver, heart, and muscle tissues (20).…”

“…Accumulation of LPC is associated with a host of diseases, including atherosclerosis, myocardial ischemia, neurodegeneration, inflammatory diseases, and diabetic complications (22). Plasma LPC concentrations were significantly elevated in insulindependent and non-insulin-dependent diabetes mellitus patients (25), diabetic retinopathy (15,17), and experimental obesity (12). Elevated LPC levels cause postprandial hyperglycemia by inhibiting glucose uptake by liver, heart, and muscle tissues (20).…”