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- Adiels, Martin, 1976, et al.
(författare)
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Acute suppression of VLDL(1) secretion rate by insulin is associated with hepatic fat content and insulin resistance
- 2007
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 50:11, s. 2356-2365
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Adiels, Martin, 1976, et al.
(författare)
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Overproduction of large VLDL particles is driven by increased liver fat content in man
- 2006
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 49:4, s. 755-65
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: We determined whether hepatic fat content and plasma adiponectin concentration regulate VLDL(1) production. METHODS: A multicompartment model was used to simultaneously determine the kinetic parameters of triglycerides (TGs) and apolipoprotein B (ApoB) in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol in ten men with type 2 diabetes and in 18 non-diabetic men. Liver fat content was determined by proton spectroscopy and intra-abdominal fat content by MRI. RESULTS: Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL(1) TG and ApoB production. However, only liver fat and plasma glucose were significant in multiple regression models, emphasising the critical role of substrate fluxes and lipid availability in the liver as the driving force for overproduction of VLDL(1) in subjects with type 2 diabetes. Despite negative correlations with fasting TG levels, liver fat content, and VLDL(1) TG and ApoB pool sizes, adiponectin was not linked to VLDL(1) TG or ApoB production and thus was not a predictor of VLDL(1) production. However, adiponectin correlated negatively with the removal rates of VLDL(1) TG and ApoB. CONCLUSIONS/INTERPRETATION: We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver. Elevated plasma glucose can further increase hepatic fat content through multiple pathways, resulting in overproduction of VLDL(1) particles and leading to the characteristic dyslipidaemia associated with type 2 diabetes.
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| 3. |
- Frondelius, P., et al.
(författare)
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Charging of atoms, clusters, and molecules on metal-supported oxides: A general and long-ranged phenomenon
- 2008
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Ingår i: Physical Review B - Condensed Matter and Materials Physics. - 2469-9950 .- 2469-9969. ; 78:8, s. 7-
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Tidskriftsartikel (refereegranskat)abstract
- The density-functional theory is used to investigate the adsorption of Au atoms, Au clusters, and NO2 molecules on transition-metal-supported oxides. As compared to unsupported oxides, the adsorbates on supported oxide films are charged and experience a higher adsorption energy. The origin of the effect is explored by considering two different oxides (MgO and Al2O3) and a range of supporting metals. Moreover, the limits of the enhancement are probed by explicit calculations for thick MgO films and low coverage. The long-range character of the phenomenon is attributed to electrostatic polarization. The absolute strength depends on several contributions and their relative importance changes with system composition.
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