The aim of this study was to investigate the effects of troglitazone (TRO) - a new insulin-sensitizing agent - on some metabolic parameters in an experimental model of hypertriglyceridemia and insulin resistance, hereditary hypertriglyceridemic rats, and to compare its effects with those of vitamin E, an antioxidant agent. Three groups of the above rats were fed diets with a high content of sucrose (70 % of energy as sucrose) for four weeks. The first group was supplemented with TRO (120 mg/kg diet), the second one with vitamin E (500 mg/kg diet), and the third group served as the control. Vitamin E supplementation did not lower serum triglycerides (2.42±0.41 vs. 3.39±0.37 mmol/l, N.S.) while TRO did (1.87±0.24 vs. 3.39±0.37 mmol/l, p<0.01). Neither TRO nor vitamin E influenced the serum levels of free fatty acids (FFA). Both drugs influenced the spectrum of fatty acids in serum phospholipids - TRO increased the levels of polyunsaturated fatty acids (PUFA) n-6 (36.04±1.61 vs. 19.65±1.56 mol %, p<0.001), vitamin E increased the levels of PUFA n-3 (13.30±0.87 vs. 6.79±0.87 mol %, p<0.001) and decreased the levels of saturated fatty acids (32.97±0.58 vs. 51.45±4.01 mol %, p<0.01). In conclusion, TRO lowered the level of serum triglycerides but vitamin E did not have this effect in hypertriglyceridemic rats. Compared with TRO, vitamin E had a different effect on the spectrum of fatty acids in serum phospholipids., Š. Chvojková, L. Kazdová, J. Divišová., and Obsahuje bibliografii
Visfatin was originally described as an adipokine with insulin mimetic effects. Recently, it was found that visfatin is identical with the Nampt (nicotinamide phosphoribosyltransferase) gene that codes for an intra- and extracellular NAD biosynthetic enzyme and is predominantly expressed outside the adipose tissue. In the current study, we found strong protein and mRNA expression of visfatin in rat heart, liver, kidney, and muscle, while the expression of visfatin in visceral fat was significantly lower and undetectable in subcutaneous fat. The insulin-mimetic effects of visfatin (extracellular form of Nampt or eNampt) are controversial and even less is known about autocrine effects of visfatin (intracellular form of Nampt or iNampt). Since liver plays a major role in glucose metabolism, we studied visfatin effects on insulin-stimulated cellular glucose uptake in Fao rat hepatocytes using RNA interference (RNAi). RNAi-mediated downregulation of visfatin expression in Fao cells was associated with significantly reduced NAD biosynthesis (0.3±0.01 vs. 0.5±0.01 mmol/h/g, P<0.05) and with significantly decreased incremental glucose uptake after stimulation with insulin when compared to controls with normal expression of visfatin (0.6±0.2 vs. 2.2±0.5 nnmol/g/2 h, P=0.02). These results provide evidence that visfatin exhibits important autocrine effects on sensitivity of liver cells to insulin action possibly through its effects on NAD biosynthesis., V. Škop ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
It has been suggested that thiazolidinediones (TZDs) ameliorate insulin resistance in muscle tissue by suppressing muscle lipid storage and the activity of novel protein kinase C (nPKC) isoforms. To test this hypothesis, we analyzed long-term metabolic effects of pioglitazone and the activation of nPKC-ε and -θ isoforms in an animal model of the metabolic syndrome, the spontaneously hypertensive rat (a congenic SHR strain with wild type Cd36 gene) fed a diet with 60 % sucrose from the age of 4 to 8 months. Compared to untreated controls, pioglitazone treatment was associated with significantly increased basal (809±36 vs 527±47 nmol glucose/g/2h, P<0.005) and insulinstimulated glycogenesis (1321±62 vs 749±60 nmol glucose/g/2h, P<0.0001) in isolated gastrocnemius muscles despite increased concentrations of muscle triglycerides (3.83±0.33 vs 2.25±0.12 μmol/g, P<0.005). Pioglitazone-treated rats exhibited significantly increased membrane/total (cytosolic plus membrane) ratio of both PKC-ε and PKC-θ isoforms compared to untreated controls. These results suggest that amelioration of insulin resistance after long-term pioglitazone treatment is associated with increased activation of PKC-ε and -θ isoforms in spite of increased lipid concentration in skeletal muscles., I. Marková ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Our aim was to assess the reaction of TNFα, resistin, leptin and adiponectin to lipid infusion. Eight healthy subjects underwent a 24-hour lasting infusion of lipid emulsion. Plasma concentrations and expressions of selected cytokines in subcutaneous fat were measured. TNFα plasma concentration did not change during the first 4 hours of hypertriglyceridemia, but a significant increase after 24 hours was detected (p<0.001 for 0; 30; 240 min vs. 24 h). Plasma concentration of resistin significantly increased at 30 min of infusion and remained elevated (p<0.01 for 0 min vs. 30; 240 min; p<0.001 for 0 min vs. 24 h). Plasma concentrations of leptin and adiponectin did not show any significant changes. Although the expression of resistin in the subcutaneous adipose tissue tended to increase, the change was not significant. Expressions of TNFα, leptin and adiponectin were unaffected. In conclusions, our results indicate that acutely induced hyperlipidemia could influence the secretion of TNFα and resistin., J. Kopecký ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Spontaneously hypertensive rats (SHR/NIH strain) harbor a deletion variant in the Cd36 fatty acid transporter and display defective fatty acid metabolism, insulin resistance and hypertension. Transgenic rescue of Cd36 in SHR ameliorates insulin resistance and improves dyslipidemia. However, the role of Cd36 in blood pressure regulation remains controversial due to inconsistent blood pressure effects that were observed with transgenic expression of Cd36 on the SHR background. In the current studies, we developed two new SHR transgenic lines, which express wild type Cd36 under the control of the universal Ef-1 promoter, and examined the effects of transgenic expression of wild type Cd36 on selected metabolic and cardiovascular phenotypes. Transgenic expression of Cd36 in the new lines was associated with significantly decreased serum fatty acids, amelioration of insulin resistance and glucose intolerance but failed to induce any consistent changes in blood pressure as measured by radiotelemetry. The current findings confirm the genetic association of defective Cd36 with disordered insulin action and fatty acid metabolism in the SHR/NIH strain and suggest that Cd36 is linked to other gene(s) on rat chromosome 4 that regulate blood pressure., M. Pravenec, V. Landa, V. Zídek, A. Musilová, L. Kazdová, N. Qi, J. Wang, E. St.Lezin, T. W. Kurtz., and Obsahuje bibliografii