ABSTRACT
The effect of acute repaglinide administration (2 mg) on postprandial glycaemia and lipaemia has been examined in 20 subjects with type 2 diabetes mellitus. Each subject received in the morning, after a 12 to 14 h fast, a standard mixed meal (total energy 783 kcal), preceded by one tablet of 2 mg repaglinide or placebo. Chylomicrons and chylomicron-deficient plasma were prepared by ultracentrifugation. Triglyceride levels in CM fraction (CM-triglycerides) in total plasma as well as in CM-deficient plasma (non-CM-triglycerides) were determined. A significant reduction in postprandial glycaemia was observed after repaglinide administration compared to placebo ( p < 0.001). Plasma concentrations of total triglycerides, CM-triglycerides, non-CM-triglycerides, free fatty acids and the other plasma lipids measured, were not significantly different between the two phases of the study. It is concluded that, in contrast to sulphonylureas, acute repaglinide administration does not improve postprandial lipaemia in patients with type 2 diabetes.
Subject(s)
Carbamates/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hyperlipidemias/blood , Piperidines/therapeutic use , Analysis of Variance , Blood Glucose/metabolism , C-Peptide/blood , Cholesterol/blood , Diabetes Mellitus, Type 2/blood , Fatty Acids, Nonesterified/blood , Glycated Hemoglobin/metabolism , Humans , Hyperlipidemias/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/blood , Kinetics , Postprandial Period , Triglycerides/bloodABSTRACT
A PAF aggregating activity corresponding to 427 +/- 91, 668 +/- 111 and 1319 +/- 217 pg/mg protein was detected when LDL was preincubated at pH 3.5 or with 4 mM PMSF or both for 30 min (treatments that inactivate PAF-AH) and then oxidized with 20 microM Cu2+ at 37 degrees C for 24 h. This molecule was characterized as PAF by its chromatographic behavior on TLC and other established methods and was further characterized as 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16: PAF) by its retention time on reverse phase HPLC and by fast atom bombardment-mass spectroscopy. Native LDL incubated under non oxidizing conditions, even when PAF-AH has been inactivated, or oxidized in the absence of PAF-AH inactivating agents or after pretreatment with 0.5 mM pBPB, does not produce detectable amounts of PAF. The kinetics of PAF formation in relation to PAF-AH activity, show that the apparent rate of PAF formation as well as its total amount depends on both the existence of oxidative conditions and the remaining PAF-AH activity the first hours following the onset of oxidation. Peroxidation of the phosphatidylcholine (PC) content of native LDL produces PAF-like aggregating activity much lower than that produced when intact LDL is oxidized and is not inhibited by BN 52021 as effectively as PAF produced by LDL peroxidation. Our results provide evidence that C16: PAF is formed during LDL peroxidation when PAF-AH has been inactivated and it does not result as a product of peroxidation of the LDL-PC content.
