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

Insulin resistance plays a role in diabetic dyslipi daemia, especially postprandial hypertriglyceridaem ia, through the overproduction of very low-density lipo pr tein (VLDL). However, the role of insulin resistance on the apoprotein profile of VLDL has no t been explored. To study the influence of insulin resistance on the VLDL proteome in the fasting and postprandial stat es. Eleven type 2 diabetes (T2DM) subjects with moderat ed 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 w ere separated and quantified with twodimensional gel electrophoresis (2D-GE) and identif ied using mass spectrometry. The VLDL proteome from the fasting and postprandial states of the con trols were compared to two groups of T2DM. Fourteen proteins with isoforms were identified from the 2DGE, 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, an d apoE, except for TTR and apoH, which were found onl y in the HIR group. In the fasting state, significa nt changes in apoA-I, apoA-IV, and apoC-II were observ ed in LIR and HIR, whereas apoC-III, apoE, and TTR were observed in HIR. In the postprandial stat e, significant alterations were found in apoA-I, ap oCII, 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 o ly associated with an increase in VLDL triglycerid Winai Dahlan et al J. Chem. Pharm. Res., 2011, 3(4):257-269 ______________________________________________________________________________ 258 levels but also with alterations in VLDL protein co mposition, which possibly affects lipoprotein metabolism in diabetic patients.