Multiple abnormalities in the transfer of phospholipids from VLDL and LDL to HDL in non‐insulin‐dependent diabetes

Abstract

Transfers or exchanges of cholesterol esters and triglycerides between lipoproteins are mediated by a specialized protein referred to as cholesteryl ester transfer protein (CETP), whereas those of phospholipids (PLs) are facilitated by both CETP and a specific phospholipid transfer protein (PLTP). In the present study, the authors compared phospholipid transfer (PLT) in normal subjects and in patients with non-insulin-dependent diabetes (NIDD), which is associated with an increased risk of atherosclerosis. PLT was measured in different recombination experiments using an isotopic assay in which the transfer of labelled PLs from very low-density lipoprotein (VLDLs) and low-density lipoproteins (LDLs) to high-density lipoproteins (HDLs) was determined. This allowed discrimination between the roles of VLDLs + LDLs, HDLs, and plasma PLT activity (PLTA). VLDL + LDL-dependent PLT, HDL-dependent PLT and PLTA were decreased in NIDD. VLDL + LDL-dependent PLT was found to be negatively correlated with the PL/apolipoprotein B ratio, whereas HDL-dependent PLT was positively correlated with the HDL2/HDL3 and PL/apolipoprotein A-I ratios and negatively correlated with the flow activation energy at the HDL surface. The HDL2/HDL3 ratio was positively correlated with PLTA but not with CETP, which confirms previous reports suggesting that PLTP might act as an HDL conversion factor. These data show that several abnormalities in PLT occur in NIDD and raise the question as to whether a lowered PLT might be a new characteristic of dis factors associated with an increased risk of atherosclerosis.

Plasma phospholipid transfer protein activity is related to insulin resistance: impaired acute lowering by insulin in obese Type II diabetic patients

“…Our study does not confirm that insulin lowers plasma CETP activity in Type II diabetic patients [11]. In contrast to the present findings, a low plasma PLTP activity has been reported in Type II diabetes but in that study the phospholipid transfer promoting action of CETP was not separated from that of PLTP [17]. An unaltered plasma PLTP activity was recently found in Type II diabetes [18].…”

Mass Concentration of Plasma Phospholipid Transfer Protein in Normolipidemic, Type IIa Hyperlipidemic, Type IIb Hyperlipidemic, and Non–Insulin-Dependent Diabetic Subjects as Measured by a Specific ELISA

“…This part of the study was hastened by recent reports addressing alterations in plasma phospholipid transfer activity in diabetic patients. However, the data are controversial, with either no alteration 44 or a significant decrease 45 in plasma phospholipid transfer activity being reported in NIDDM, as assessed by distinct isotopic activity assays. In addition, circumstantial evidence in favor of increased PLTP-mediated conversion of HDL 3 to HDL 2 in plasma from hypertriglyceridemic NIDDM patients compared with normolipidemic controls has recently been reported.…”

The transfer of VLDL-associated phospholipids to activated platelets depends upon cytosolic phospholipase A2 activity

“…14 C]PAPC (1 mCi/10 mmol lipoprotein PL) as reported previously (16). The desired amount of radioactive label was dried under nitrogen, solubilized in ethanol, and added to VLDL under vortexing.…”

“…Phospholipid transfer protein (PLTP) activity was determined using an in vitro assay in which we measured the transfer of radiolabeled PL from VLDL to HDL using delipidated plasma as the source of PLTP, as described previously (16). Basal as well as PLTP-facilitated PL transfers were measured in the absence or presence of cPLA 2 inhibitors at the same concentrations as those used with platelets.…”