Original Articles: 2011 Vol: 3 Issue: 4
The influence of insulin resistance on very low-density lipoprotein proteome changes in type 2 diabetes after oral high-fat meal loading: A pilot study
Abstract
Insulin resistance plays a role in diabetic dyslipidaemia, especially postprandial hypertriglyceridaemia,
through the overproduction of very low-density lipoprotein (VLDL). However, the role of insulin resistance on the apoprotein profile of VLDL has not been explored. To study the influence of insulin resistance on the VLDL proteome in the fasting and postprandial states. Eleven type 2 diabetes (T2DM) subjects with moderated metabolic control (HbA1c <8%) were classified as lower insulin resistance, LIR (HOMA-IR<2.5, n=5), and higher insulin resistance, HIR (HOMA-IR 2.5-5.0, n=6), and were compared to 10 non-diabetic controls. After 12 hours of fasting, the subjects consumed a fat-rich meal. Both before the meal and 4 hours after the meal, blood samples were taken to study the VLDL proteome. VLDL-associated proteins were separated and quantified with twodimensional gel electrophoresis (2D-GE) and identified using mass spectrometry. The VLDL proteome from the fasting and postprandial states of the controls were compared to two groups of T2DM. Fourteen proteins with isoforms were identified from the 2D-GE, including the novel protein transthyretin (TTR). There were significant alterations (p<0.05) in all groups among apoA-I, apoA-IV, apoC-II, apoC-III, and apoE, except for TTR and apoH, which were found only in the HIR group. In the fasting state, significant changes in apoA-I, apoA-IV, and apoC-II were observed in LIR and HIR, whereas apoC-III, apoE, and TTR were observed in HIR. In the postprandial state, significant alterations were found in apoA-I, apoCII, apoC-III, apoE, and TTR in LIR and HIR, except for apoH, which was found only in the HIR group. These data suggest that insulin resistance is not only associated with an increase in VLDL triglyceride levels but also with alterations in VLDL protein composition, which possibly affects lipoprotein metabolism in diabetic patients.