Evidence of increased secretion of apolipoprotein B-48-containing lipoproteins in subjects with type 2 diabetes

Abstract

Patients with type 2 diabetes have high levels of triglyceride-rich lipoproteins (TRLs), including apolipoprotein B-48 (apoB-48)-containing TRLs of intestinal origin, but the mechanism leading to overaccumulation of these lipoproteins remains to be fully elucidated. Therefore, the objective of this study was to examine the in vivo kinetics of TRL apoB-48 and VLDL, intermediate density lipoprotein (IDL), and LDL apoB-100 in type 2 diabetic subjects (n 5 11) and nondiabetic controls (n 5 13) using a primedconstant infusion of L-[5,5,5-D 3 ]leucine for 12 h in the fed state. Diabetic subjects had significantly higher fasting glycemia, higher fasting insulinemia, higher plasma triglyceride, and lower HDL-cholesterol levels than controls. Compared with controls, diabetic subjects had increased TRL apoB-48, VLDL apoB-100, and IDL apoB-100 pool sizes as a result of increased production rates (PRs) and reduced fractional catabolic rates of these lipoprotein subfractions. Furthermore, multiple linear regression analyses revealed that the diabetic/control status was an independent predictor of TRL apoB-48 PR and represented nearly 35% of its variance. These results suggest that the overaccumulation of TRLs seen in patients with type 2 diabetes is attributable to increased PRs of both intestinally derived apoB-48-containing lipoproteins and TRL apoB-100 of hepatic origin and to decreased catabolism of these

Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance

“…The plasma TRL concentrations were signifi cantly higher in the subjects with IR because these subjects had higher PRs of intestinal and hepatic TRL particles as well as lower clearance rates. This study enhances the data from previous studies ( 2,6 ) that revealed an oversecretion of TRL apoB-48 in subjects with IR. The current study provides new evidence, however, that key genes involved in intestinal lipid and lipoprotein metabolism are downregulated in subjects with IR compared with IS controls.…”

Pharmacological Targeting of the Atherogenic Dyslipidemia Complex: The Next Frontier in CVD Prevention Beyond Lowering LDL Cholesterol

“…Although there are some differences in the regulation of VLDL and chylomicron particle production, similar mechanisms are also likely to be involved in enhancing chylomicron production in the intestine (43,44). Thus, the production of intestinally derived TRL apoB-48 is also increased in insulin resistance (45), obesity (46), and T2D (47,48), and chylomicron TG secretion is increased in metabolic syndrome (49).…”

Molecular processes that handle — and mishandle — dietary lipids

“…In intestinal insulin resistance and overt diabetes, the increase in apoB 48 secretion noted above implies a higher particle number. Insulin resistance also enhances endogenous intestinal synthesis of fatty acids, triglycerides, and cholesteryl esters that contribute to CM overproduction (15,67) and downstream atherogenic effects (Table 1 and ref. 7).…”