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

Adiels, Martin; Westerbacka, Jukka; Soro‐Paavonen, Aino; Häkkinen, Anna‐Maija; Vehkavaara, Satu; Caslake, Muriel; Packard, Chris J.; Olofsson, Sven-Olof; Yki‐Järvinen, Hannele; Taskinen, Marja‐Riitta; Borén, Jan

doi:10.1007/s00125-007-0790-1

Cited by 167 publications

(145 citation statements)

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“…However, studies have also shown an association between liver fat content and the postprandial increase in ApoB-100 [28,29], indicating that endogenous VLDL-TAG secretion may also contribute to postprandial lipaemia in type 2 diabetes. Despite the wide range of different tracers and kinetic models employed to study VLDL-TAG kinetics, results in healthy individuals have convincingly shown that acute experimental hyperinsulinaemia decreases hepatic production of VLDL-ApoB [12,14,[30][31][32][33] and VLDL-TAG [10,12,14,30,31], primarily through suppression of VLDL 1 (rather than VLDL 2 ) production [12,32,33]. Insulin-mediated suppression of VLDL-TAG secretion may partly be attributed to diminished hepatic NEFA delivery secondary to suppression of adipose tissue lipolysis [34].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, acute hyperinsulinaemia leads to a rapid inhibition of hepatic VLDL-TAG secretion, as evidenced from data stemming from in vitro studies, animal models and human studies [6][7][8]10]. Some previous studies have shown that diabetic patients fail to downregulate secretion of large VLDL (VLDL 1 ) in an experimental setting with high-dose insulin infusion [11,12], whereas we reported a preserved suppressive effect of hyperinsulinaemia on VLDL-TAG secretion [7]. The impact of meal-induced hyperinsulinaemia, on the other hand, is less well understood.…”

Section: Introductionmentioning

confidence: 99%

“…The impact of meal-induced hyperinsulinaemia, on the other hand, is less well understood. Knowledge regarding postprandial changes in VLDL kinetics is mostly indirect and derived from studies using the hyperinsulinaemic clamp to mimic the rapid increase in insulin levels observed after a meal [6,10,[12][13][14]. This approach has the obvious advantage that steady-state kinetics can be applied to tracer studies, yielding reproducible estimates of both VLDL-TAG production and insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

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Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men

et al. 2012

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Aims/hypothesis Type 2 diabetes is characterised by insulin resistance and increased post-absorptive secretion of VLDLtriacylglycerol (VLDL-TAG). Whether postprandial suppression of endogenous VLDL-TAG secretion is abnormala finding that would link hyperlipidaemia and type 2 diabetes-remains unclear. Methods Eight type 2 diabetic men and eight healthy men were studied before and after a fat-free test meal (40% of resting energy expenditure). VLDL-TAG kinetics were assessed using a primed-constant infusion of ex vivo labelled [1-14 C]triolein VLDL-TAG using non-steadystate calculations. Results Type 2 diabetic men had a higher basal VLDL-TAG secretion rate and concentration than healthy men (mean±SD secretion rate 137±61 vs 78±30 μmol/min, respectively [p00.03]; median concentration 1.03 [range 0.58-1.75] vs 0.33 [0.13-1.14]mmol/l, respectively [p<0.01]). Postprandially, the VLDL-TAG secretion rate decreased in healthy men (p<0.01), but remained unchanged in diabetic men (p00.47). The VLDL-TAG concentration increased in diabetic men and decreased in healthy men postprandially (p<0.05). The difference in VLDL-TAG secretion rate between the two groups approached significance (p00.06) and the relative change in VLDL-TAG secretion rate was significantly different (p00.01) between the two groups. Basal VLDL-TAG clearance was significantly lower in diabetic men (diabetic men 133 [49-390]ml/min; healthy controls 215 ml/min [p<0.05]). After meal ingestion, clearance decreased in healthy men (p00.03), but was unchanged in diabetic men (p00.58). Conclusions/interpretation Obese type 2 diabetic men have impaired postprandial suppression of VLDL-TAG secretion compared with lean healthy men, contributing to their postprandial lipaemia and hypertriacylglycerolaemia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men

et al. 2012

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“…Adiels et al [15] carried out a study into the suppression of hepatic VLDL1 secretion by insulin, and of particular use to us VLDL-TAG is measured. This secretion of VLDL1 relates in our model to the release of TAG from the liver; although the other types of lipoprotein are involved in TAG transport, VLDL1 is responsible for the majority of the flux through the insulin inhibited hepatic secretion pathway.…”

Section: Parameter Assessmentmentioning

confidence: 99%

“…Although it has been shown that there is a strong correlation between obesity and fatty liver disease [14] it is not known if fatty liver disease is the cause or effect of insulin resistance. It has been shown that post-prandial hepatic triglyceride release is higher in people with fatty liver disease than healthy people although the basal secretion rate is the same, indicating that it is not a higher fat presence in the liver which causes the increased output but rather insulin resistance [15].…”

Section: Introductionmentioning

confidence: 99%

A Mathematical Model of the Human Metabolic System and Metabolic Flexibility

et al. 2014

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A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. Abstract In healthy subjects some tissues in the human body display metabolic flexibility, by this we mean the ability for the tissue to switch its fuel source between predominantly carbohydrates in the post prandial state and predominantly fats in the fasted state. Many of the pathways involved with human metabolism are controlled by insulin, and insulin-resistant states such as obesity and type-2 diabetes are characterised by a loss or impairment of metabolic flexibility.In this paper we derive a system of 12 first-order coupled differential equations that describe the transport between and storage in different tissues of the human body. We find steady state solutions to these equations and use these results to nondimensionalise the model. We then solve the model numerically to simulate a healthy balanced meal and a high fat meal and we discuss and compare these results. Our numerical results show good agreement with experimental data where we have data available to us and the results show behaviour that agrees with intuition where we currently have no data with which to compare.

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Pathogenesis of nonalcoholic fatty liver disease (NAFLD)

Yki‐Järvinen

2015

International Textbook of Diabetes Mellitus

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

Cited by 167 publications

References 48 publications

Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men

Postprandial VLDL-triacylglycerol secretion is not suppressed in obese type 2 diabetic men

A Mathematical Model of the Human Metabolic System and Metabolic Flexibility

Pathogenesis of nonalcoholic fatty liver disease (NAFLD)

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