Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia
Artikel i vetenskaplig tidskrift, 2005

OBJECTIVE: We sought to compare the synthesis and metabolism of VLDL1 and VLDL2 in patients with type 2 diabetes mellitus (DM2) and nondiabetic subjects. METHODS AND RESULTS: We used a novel multicompartmental model to simultaneously determine the kinetics of apolipoprotein (apo) B and triglyceride (TG) in VLDL1 and VLDL2 after a bolus injection of [2H3]leucine and [2H5]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Our results show that the overproduction of VLDL particles in DM2 is explained by enhanced secretion of VLDL1 apoB and TG. Direct production of VLDL2 apoB and TG was not influenced by diabetes per se. The production rates of VLDL1 apoB and TG were closely related, as were the corresponding pool sizes. VLDL1 and VLDL2 compositions did not differ in subjects with DM2 and controls, and the TG to apoB ratio of newly synthesized particles was very similar in the 2 groups. Plasma glucose, insulin, and free fatty acids together explained 55% of the variation in VLDL1 TG production rate. CONCLUSIONS: Insulin resistance and DM2 are associated with excess hepatic production of VLDL1 particles similar in size and composition to those in nondiabetic subjects. We propose that hyperglycemia is the driving force that aggravates overproduction of VLDL1 in DM2.

Cholesterol

Deuterium/diagnostic use

Glycerol/pharmacokinetics

Blood Glucose

Hyperglycemia/complications/*metabolism

Insulin Resistance

Male

Dyslipidemias/complications/*metabolism

Type 2/complications/*metabolism

HDL/blood

Leucine/pharmacokinetics

Triglycerides/blood

Adult

Diabetes Mellitus

Apolipoproteins B/blood

Cholesterol

VLDL/*biosynthesis/*blood

Humans

Författare

Martin Adiels

Chalmers, Matematiska vetenskaper

Göteborgs universitet

Jan Borén

Göteborgs universitet

M. J. Caslake

Helsinki University Central Hospital

P. Stewart

Helsinki University Central Hospital

Aina Soro

Glasgow Royal Infirmary

J. Westerbacka

Glasgow Royal Infirmary

Bernt Wennberg

Chalmers, Matematiska vetenskaper, Matematik

Göteborgs universitet

Sven-Olof Olofsson

Göteborgs universitet

C. Packard

Helsinki University Central Hospital

M. R. Taskinen

Glasgow Royal Infirmary

Arteriosclerosis, Thrombosis, and Vascular Biology

1079-5642 (ISSN) 1524-4636 (eISSN)

Vol. 25 1697-703

Ämneskategorier

Dermatologi och venereologi

Beräkningsmatematik

DOI

10.1161/01.ATV.0000172689.53992.25