Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance

Diabetologia. 2007 Nov;50(11):2356-65. doi: 10.1007/s00125-007-0790-1. Epub 2007 Sep 12.


Aims/hypothesis: Overproduction of VLDL(1) seems to be the central pathophysiological feature of the dyslipidaemia associated with type 2 diabetes. We explored the relationship between liver fat and suppression of VLDL(1) production by insulin in participants with a broad range of liver fat content.

Methods: A multicompartmental model was used to determine the kinetic parameters of apolipoprotein B and TG in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol during a hyperinsulinaemic-euglycaemic clamp in 20 male participants: eight with type 2 diabetes and 12 control volunteers. The participants were divided into two groups with low or high liver fat. All participants with diabetes were in the high liver-fat group.

Results: The results showed a rapid drop in VLDL(1)-apolipoprotein B and -triacylglycerol secretion in participants with low liver fat during the insulin infusion. In contrast, participants with high liver fat showed no significant change in VLDL(1) secretion. The VLDL(1) suppression following insulin infusion correlated with the suppression of NEFA, and the ability of insulin to suppress the plasma NEFA was impaired in participants with high liver fat. A novel finding was an inverse response between VLDL(1) and VLDL(2) secretion in participants with low liver fat: VLDL(1) secretion decreased acutely after insulin infusion whereas VLDL(2) secretion increased.

Conclusions/interpretation: Insulin downregulates VLDL(1) secretion and increases VLDL(2) secretion in participants with low liver fat but fails to suppress VLDL(1) secretion in participants with high liver fat, resulting in overproduction of VLDL(1). Thus, liver fat is associated with lack of VLDL(1) suppression in response to insulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen
  • Adipose Tissue / anatomy & histology*
  • Adipose Tissue / physiology
  • Adult
  • Apolipoproteins B / blood
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Fatty Acids, Nonesterified / metabolism
  • Humans
  • Insulin / blood
  • Insulin / physiology*
  • Insulin Resistance / physiology*
  • Kinetics
  • Lipoproteins, VLDL / antagonists & inhibitors
  • Lipoproteins, VLDL / metabolism*
  • Liver / anatomy & histology*
  • Liver / metabolism
  • Male
  • Middle Aged
  • Reference Values


  • Apolipoproteins B
  • Fatty Acids, Nonesterified
  • Insulin
  • Lipoproteins, VLDL