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- Ruge, T., et al.
(författare)
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Acute hyperinsulinemia raises plasma interleukin-6 in both nondiabetic and type 2 diabetes mellitus subjects, and this effect is inversely associated with body mass index
- 2009
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Ingår i: Metabolism. - 1532-8600 .- 1532-8600. ; 58:6, s. 860-6
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Tidskriftsartikel (refereegranskat)abstract
- Hyperinsulinemia is a characteristic of type 2 diabetes mellitus (T2DM) and is believed to play a role in the low-grade inflammation seen in T2DM. The main aim was to study the effect of hyperinsulinemia on adipokines in individuals with different levels of insulin resistance, glycemia, and obesity. Three groups of sex-matched subjects were studied: young healthy subjects (YS; n = 10; mean age, 26 years; body mass index [BMI], 22 kg/m(2)), patients with T2DM (DS; n = 10; 61 years; BMI, 27 kg/m(2)), and age- and BMI-matched controls to DS (CS; n = 10; 60 years; BMI, 27 kg/m(2)). Plasma concentrations of adipokines were measured during a hyperinsulinemic euglycemic clamp lasting 4 hours. Moreover, insulin-stimulated glucose uptake in isolated adipocytes was analyzed to address adipose tissue insulin sensitivity. Plasma interleukin (IL)-6 increased significantly (P < or = .01) in all 3 groups during hyperinsulinemia. However, the increase was smaller in both DS (P = .06) and CS (P < .05) compared with YS (approximately 2.5-fold vs approximately 4-fold). A significant increase of plasma tumor necrosis factor (TNF) alpha was observed only in YS. There were only minor or inconsistent effects on adiponectin, leptin, and high-sensitivity C-reactive protein levels during hyperinsulinemia. Insulin-induced rise in IL-6 correlated negatively to BMI (P = .001), waist to hip ratio (P = .05), and baseline (fasting) insulin (P = .03) and IL-6 (P = .02) levels and positively to insulin-stimulated glucose uptake in isolated adipocytes (P = .07). There was no association with age or insulin sensitivity. In a multivariate analysis, also including T2DM/no T2DM, an independent correlation (inverse) was found only between BMI and fold change of IL-6 (r(2) = 0.41 for model, P < .005). Hyperinsulinemia per se can produce an increase in plasma IL-6 and TNFalpha, and this can potentially contribute to the low-grade inflammation seen in obesity and T2DM. However, obesity seems to attenuate the ability of an acute increase in insulin to further raise circulating levels of IL-6 and possibly TNFalpha.
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| 2. |
- Ruge, Toralph, et al.
(författare)
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Effects of hyperinsulinemia on lipoprotein lipase, angiopoietin-like protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus
- 2012
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Ingår i: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 61:5, s. 652-660
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Tidskriftsartikel (refereegranskat)abstract
- Our aims were to compare the systemic effects of insulin on lipoprotein lipase (LPL) in tissues from subjects with different degrees of insulin sensitivity. The effects of insulin on LPL during a 4-hour hyperinsulinemic, euglycemic clamp were studied in skeletal muscle, adipose tissue, and postheparin plasma from young healthy subjects (YS), older subjects with type 2 diabetes mellitus (DS), and older control subjects (CS). In addition, we studied the effects of insulin on the expression of 2 recently recognized candidate genes for control of LPL activity: angiopoietin-like protein 4 (ANGPTL4) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. As an effect of insulin, LPL activity decreased by 20% to 25% in postheparin plasma and increased by 20% to 30% in adipose tissue in all groups. In YS, the levels of ANGPTL4 messenger RNA in adipose tissue decreased 3-fold during the clamp. In contrast, there was no significant change in DS or CS. Regression analysis showed that the ability of insulin to reduce the expression of ANGPTL4 was positively correlated with M-values and inversely correlated with factors linked to the metabolic syndrome. Expression of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 tended to be higher in YS than in DS or CS, but the expression was not affected by insulin in any of the groups. Our data imply that the insulin-mediated regulation of LPL is not directly linked to the control of glucose turnover by insulin or to ANGPTL4 expression in adipose tissue or plasma. Interestingly, the response of ANGPTL4 expression in adipose tissue to insulin was severely blunted in both DS and CS.
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