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01.11.2007 | Article

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

verfasst von: M. Adiels, J. Westerbacka, A. Soro-Paavonen, A. M. Häkkinen, S. Vehkavaara, M. J. Caslake, C. Packard, S. O. Olofsson, H. Yki-Järvinen, M. R. Taskinen, J. Borén

Erschienen in: Diabetologia | Ausgabe 11/2007

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Abstract

Aims/hypothesis

Overproduction of VLDL₁ 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 VLDL₁ 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 VLDL₁ and VLDL₂ after a bolus of [²H₃]leucine and [²H₅]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 VLDL₁-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 VLDL₁ secretion. The VLDL₁ 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 VLDL₁ and VLDL₂ secretion in participants with low liver fat: VLDL₁ secretion decreased acutely after insulin infusion whereas VLDL₂ secretion increased.

Conclusions/interpretation

Insulin downregulates VLDL₁ secretion and increases VLDL₂ secretion in participants with low liver fat but fails to suppress VLDL₁ secretion in participants with high liver fat, resulting in overproduction of VLDL₁. Thus, liver fat is associated with lack of VLDL₁ suppression in response to insulin.

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Titel: Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance
verfasst von: M. Adiels
J. Westerbacka
A. Soro-Paavonen
A. M. Häkkinen
S. Vehkavaara
M. J. Caslake
C. Packard
S. O. Olofsson
H. Yki-Järvinen
M. R. Taskinen
J. Borén
Publikationsdatum: 01.11.2007
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 11/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-007-0790-1

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

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

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