Diabetologia

, Volume 40, Issue 4, pp 454-462

Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM

  • R. MalmströmAffiliated withDepartment of Medicine, University of Helsinki, Helsinki, Finland
  • , C. J. PackardAffiliated withDepartment of Pathological Biochemistry, Royal Infirmary, Glasgow, Scotland, UK
  • , M. CaslakeAffiliated withDepartment of Pathological Biochemistry, Royal Infirmary, Glasgow, Scotland, UK
  • , D. BedfordAffiliated withDepartment of Pathological Biochemistry, Royal Infirmary, Glasgow, Scotland, UK
  • , P. StewartAffiliated withDepartment of Pathological Biochemistry, Royal Infirmary, Glasgow, Scotland, UK
  • , H. Yki-JärvinenAffiliated withDepartment of Medicine, University of Helsinki, Helsinki, Finland
  • , J. ShepherdAffiliated withDepartment of Pathological Biochemistry, Royal Infirmary, Glasgow, Scotland, UK
  • , M.-R. TaskinenAffiliated withDepartment of Medicine, University of Helsinki, Helsinki, Finland

Summary

Insulin administration to healthy subjects inhibits the production of very low density lipoprotein (VLDL)1 (Svedbergs flotation (Sf) rate 60–400) without affecting that of VLDL2 (Sf 20–60) subclass. This study was designed to test whether this hormonal action is impaired in non-insulin-dependent diabetes mellitus (NIDDM). We studied six men with NIDDM (age 53 ± 3 years, body mass index 27.0 ± 1.0 kg/m2, plasma triglycerides 1.89 ± 0.22 mmol/l) during an 8.5 h infusion of saline (control) and then in hyperinsulinaemic (serum insulin ∼ 540 pmol/l) conditions during 8.5 h infusions of glucose and insulin to give either hyper- and normoglycaemic conditions. [3-2H]-leucine was used as tracer and kinetic constants derived using a non-steady-state multicompartmental model. Compared to the control study, patients with NIDDM reduced VLDL1 apo B production by only 3 ± 8 % after 8.5 h of hyperinsulinaemia (701 ± 102 vs 672 ± 94 mg/day respectively, NS) in hyperglycaemic conditions and by 9 ± 21 % under normoglycaemic conditions (603 ± 145 mg/day). In contrast, in normal subjects insulin induced a 50 ± 15 % decrement in VLDL1 apo B production (p < 0.05). Direct synthesis of VLDL2 apo B in patients with NIDDM was not markedly affected by insulin. We conclude that a contributory factor to hypertriglyceridaemia in NIDDM is the inability of insulin to inhibit acutely the release of VLDL1 from the liver, despite efficient suppression of serum non-esterfied fatty acids. [Diabetologia (1997) 40: 454–462]

Keywords Apolipoprotein B stable isotopes insulin resistance non-esterified fatty acids cholesterol.