Increased hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 in NIDDM

Abstract

We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable isotope gas-chromatography mass-spectrometry method in six patients with non-insulin-dependent diabetes mellitus (NIDDM) (four males, two females, age 57.5 +/- 2.2 years (mean +/- SEM), weight 88.2 +/- 5.5 kg, glycated haemoglobin (HbA1) 8.5 +/- 0.5%, plasma total cholesterol concentration 5.7 +/- 0.5 mmol/l, triglyceride 3.8 +/- 0.9 mmol/l, high-density lipoprotein (HDL) cholesterol 1.0 +/- 0.1 mmol/l) and six non-diabetic subjects matched for age, sex and weight (four males, two females, age 55.7 +/- 2.8 years, weight 85.8 +/- 5.6 kg, HbA1 6.5 +/- 0.1%, plasma total cholesterol concentration 5.7 +/- 0.5 mmol/l, triglyceride 1.2 +/- 0.1 mmol/l, HDL cholesterol 1.4 +/- 0.1 mmol/l). HbA1, plasma triglyceride and mevalonic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the diabetic patients than in the non-diabetic subjects (p = 0.006, p = 0.02 and p = 0.004, respectively). VLDL apoB absolute secretion rate was significantly higher in the diabetic patients compared with the non-diabetic subjects (2297 +/- 491 vs 921 +/- 115 mg/day, p < 0.05), but there was no significant difference in the fractional catabolic rate of VLDL apoB. There was a positive correlation between VLDL apoB secretion rate and (i) fasting C-peptide (r = 0.84, p = 0.04) and (ii) mevalonic acid concentration (r = 0.83, p < 0.05) in the diabetic patients but not in the non-diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of Amino Acids and Insulin to Protein Anabolism During Meal Absorption

“…In fact, the isotopic enrichment/SA of plasma proteins reaches a steady state when the precursor (leucyl-tRNA enrichment) and product have the same value (50). In this regard, the use of apoB-100 offers several methodological advantages: 1) apoB-100 is almost exclusively synthesized by the liver and secreted as VLDL (51), 2) the time required to completely change the plasma protein pool (12,(52)(53)(54) is relatively short (5-6 h) (Fig. 3), and 3) after secretion, VLDLs are continuously converted to LDLs (51); consequently, at plateau, the enrichment/SA of leucine bound to apoB-100 is representative of the most recently secreted protein, i.e., reflects eventual changes in the enrichment/SA of its tRNA (12).…”

New insights into the pathophysiology of dyslipidemia in type 2 diabetes

“…154,155 This is related to insulin resistance and type 2 diabetes, and probably explains (at least partly) the dyslipidaemia that is observed in subjects with insulin resistance and type 2 diabetes. [156][157][158][159] Mechanisms leading to overproduction of VLDL in type 2 diabetes…”

Asymptomatic individuals with high HDL-C levels overexpress ABCA1 and ABCG1 and present miR-33a dysregulation in peripheral blood mononuclear cells

“…The dyslipidemia observed in insulin resistance states is usually associated with increased hepatic production of VLDL (Kissebah et al, 1982;Duvillard et al, 2000;Ouguerram et al, 2003;Cummings et al, 1995), leading to altered HDL composition through CETP and hepatic lipase activities. Small, dense HDL particles produced are rapidly catabolized, and consequently HDL-C levels are decreased (Rashid et al, 2003).…”