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

Abstract

Among other factors, high density lipoprotein (HDL) metabolism and remodelling is governed by cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) [1±7]. CETP catalyses the transfer of cholesteryl esters (CE), triglycerides (TG) and phospholipids between HDL and very low + low density lipoproteins (VLDL + LDL). PLTP specifically facilitates the transfer of phospholipids between lipoproteins and is able to convert HDL 3 into small and large HDL particles [5]. During this HDL remodelling small, apolipoprotein (apo) AI-rich, preb-HDL particles are generated [6]. Such particles could act as initial acceptors of free choles- Diabetologia (1998) Summary Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) have important functions in high density lipoprotein (HDL) metabolism. We determined the association of plasma CETP and PLTP activities (measured with exogenous substrate assays) with insulin resistance, plasma triglycerides (TG) and non-esterified fatty acids (NEFA), and assessed the lipid transfer protein response to insulin during a 6±7 h hyperinsulinaemic euglycaemic clamp in non-obese and obese healthy subjects and patients with Type II (non-insulin-dependent) diabetes mellitus (n = 8 per group). Plasma PLTP activity was higher in obese healthy subjects and obese Type II diabetic patients compared with non-obese healthy subjects (p < 0.05 to 0.01) and was correlated with insulin resistance, plasma TG and NEFA (p = 0.02 to < 0.01). In non-obese healthy subjects, insulin decreased plasma TG and increased the HDL cholesteryl ester (CE)/TG ratio (p < 0.01 compared with saline infusion). Plasma PLTP activity fell by 14 % at the end of the clamp (p < 0.01 compared with saline) but CETP activity did not change.The decreases in plasma NEFA, TG and PLTP activity and the rise in HDL CE/TG were smaller in obese Type II diabetic patients than in non-obese healthy subjects (p < 0.01 for all). Baseline HDL CE/TG was negatively correlated with plasma TG (p < 0.001, n = 32) and PLTP activity (p < 0.01) but not with CETP activity. Likewise, the rise in HDL CE/TG during the clamp was related to the fall in plasma TG (p < 0.001) and in PLTP activity (p < 0.02). It is concluded that plasma PLTP, but not CETP, is regulated by insulin in an acute setting. High plasma PLTP activity is associated with insulin resistance in conjunction with altered NEFA and triglyceride metabolism. High plasma TG and PLTP activity have coordinate effects on HDL metabolism. [Diabetologia (1998) 41: 929±934]

Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2

“…Similarily, for type 2 diabetic patients unchanged, 19,20 decreased 17,18 and accelerated CETP activities 22 have been reported. In hyperinsulinemic euglycemic clamp studies 19,20 decreased PLTP activity after insulin infusion was reported in both, healthy and type 2 diabetic subjects. Similar results were found in a hyperglycemia-induced hyperinsulinemia study in healthy humans.…”

“…14 -16 In several clinical studies the influence of insulin infusion on lipid transfer protein activities was investigated with, however, partly conflicting results. 17 -21 In healthy subjects insulin infusion appeared not to change CETP activity in some studies, 18,20,21 while in others 13,19 it decreased CETP activity. Similarily, for type 2 diabetic patients unchanged, 19,20 decreased 17,18 and accelerated CETP activities 22 have been reported.…”

“…17 -21 In healthy subjects insulin infusion appeared not to change CETP activity in some studies, 18,20,21 while in others 13,19 it decreased CETP activity. Similarily, for type 2 diabetic patients unchanged, 19,20 decreased 17,18 and accelerated CETP activities 22 have been reported. In hyperinsulinemic euglycemic clamp studies 19,20 decreased PLTP activity after insulin infusion was reported in both, healthy and type 2 diabetic subjects.…”

The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients

“…In this study we have found that overall phospholipid transfer tended to be lower in the diabetic subjects than in controls, but whereas cholesteryl ester transfer increased postprandially phospholipid transfer decreased. The postprandial fall in PLTP activity is unexplained but likely be related to insulin sensitivity [40][41][42][43].…”

Adipocyte and erythrocyte plasma membrane phospholipid composition and hyperinsulinemia: a study in nondiabetic and diabetic obese women

“…These changes could be mediated by cholesteryl Hyperinsulinemia, adipocyte and erythrocyte phospholipids N Zeghari et al ester transfer protein (CETP), which has a role in the selective uptake of HDL cholesteryl esters by human adipocytes, 42 or by phospholipid transfer protein (PLTP). 43 CETP and PLTP activities are elevated in obesity 44 and in insulin resistance 45 as well as the HDL binding to adipocytes. 19 The hormone status may be also important.…”