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
Patients with obesity and type 2 diabetes often display high levels of the anti-diabetic factor fibroblast growth factor-21 (FGF21), suggesting that the overproduction of FGF21 may result from increased adiposity in an attempt by white adipose tissue (WAT) to counteract insulin resistance. However, the production of FGF21 diabetes in the absence of WAT has not been examined. In this study, we investigated the effects of lipodystrophy in A-ZIP F-1 mice on FGF21 production in relation to diabetes. A-ZIP F-1 mice displayed high FGF21 plasma levels resulting from enhanced FGF21 mRNA expression in the liver. Concomitant enhancement of FGF21 receptor (FGFR1) and glucose transporter 1 (GLUT-1) mRNA expression was observed in the muscles of A-ZIP F-1 mice. Furthermore, the activation of hypothalamic NPY and AgRP mRNA expression positively correlated with plasma levels of FGF21 but not active ghrelin. Our study demonstrates that an increased FGF21 plasma level in lipodystrophic A-ZIP F-1 mice results mainly from up-regulated liver production but does not suffice to overcome the lipodystrophy-induced severe type 2-diabetes and insulin resistance in the liver linked to the augmented liver fat deposition., A. Špolcová, M. Holubová, B. Mikulášková, V. Nagelová, A. Štofková, Z. Lacinová, J. Jurčovičová, M. Haluzík, L. Maletínská, B. Železná., and Obsahuje bibliografii
We assessed the effect of the previously uncovered gap junctio n protein alpha 8 (Gja8) mutation present in spontaneously hypertensive rat - dominant cataract (SHR - Dca ) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR - Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and diastolic blood pressures in SHR - Dca compared with SHR (P<0.01 and P<0.05 , respectively; repeated measures analysis of variance (ANOVA)). With immunohistochemistry, we were able to localize Gja8 in heart, kidney, aorta, liver, and lungs, mostly in endothelium; with no differences in expression between strains. SHR - Dca rats showed decreased body weight, high-density lipoprotein cholesterol concentrations and basa l insulin sensitivity in muscle. There were 21 transc ripts common to the sets of 303 transcripts in kidney and 487 in heart showing >1.2-fold difference in expression between SHR and SHR - Dca. Tumor necrosis factor was the most significant upstream regulato r and glial cell-derived neurotrophic factor family ligand-receptor interactions was the common enriched and downregulated canonical pathway both in heart and kidney of SHR - Dca. The connexin 50 mutation L7Q lowers blood pressure in the SHR - Dca strain, decr eases high-density lipoprotein cholesterol, and leads to substantial transcriptome changes in heart and kidney., O. Šeda, F. Liška, M. Pravenec, Z. Vernerová, L. Kazdová, D. Křenová, V. Zídek, L. Šedová, M. Krupková, V. Křen., and Obsahuje bibliografii
Insulin resistance associated with dyslipidemia enhances cardiovascular risk. Several atherogenic indexes have been suggested to give more precise information about the risk. The aim of our study was to estimate, which atherogenic index correlates better with parameters of insulin resistance. Furthermore, we compared the parameters of lipid metabolism and insulin resistance between smokers and non-smokers. In our cross-sectional study we enrolled 729 patients with dyslipidemia which were divided into two groups - non-smokers (586) and smokers (143). We measured lipid profile, parameters of insulin resistance (fasting glycemia, insulin, HOMA-IR, C-peptide, proinsulin) and calculated atherogenic indexes - atherogenic index of plasma (log (TAG/HDL-C), AIP), ApoB/ApoA1 index and nonHDL-C. AIP was found out to show stronger correlations with parameters of insulin resistance (p<0.001, correlation coefficients ranging between 0.457 and 0.243) than other indexes (ApoB/ApoA1 or nonHDL cholesterol). AIP correlated with parameters of insulin resistance both in smokers and nonsmokers, but after adjustment (for age, body mass index, waist circumference) persisting only in non-smokers. Smokers had a wider waist circumference and a proatherogenic lipid profile. Smoking increases the risk of developing metabolic syndrome. AIP can be used in daily praxis for predicting insulin resistance in patients with dyslipidemia, predominantly in non-smokers., L'. Cibičková, D. Karásek, K. Langová, H. Vaverková, J. Orság, J. Lukeš, D. Novotný., and Obsahuje bibliografii
This study aimed to examine relationships between DHEA(S), anthropometric parameters, oral glucose tolerance test derived data and lipid spectra in a Czech non-diabetic population. 380 healthy volunteers both with and without a family history of diabetes type 2 (DM2) were en rolled into the study (women: n=235, age 28.9±9.4 years, BMI 22.3±4.5 kg/m2, men: n=145, age 32.3±10.0 years, BMI 24.7±3.6 kg/m2). Spearman’s correlations (both without and with the adjustment for age, age and BMI), as well as ANCOVA were used. Non-adjusted data showed many “beneficial” correlations between DHEA(S) and both anthropometric and metabolic variables. Statistical analysis revealed that almost all correlations of DHEA(S) to adiposity and fat distribution in men as well as in women disappeared after the adjustment. There are, however, differences between men and women in the correlation of DHEA(S) to insulin sensitivity and lipid levels. The use of hormonal contraceptives (COC) is also an important factor in this relationship. In men and also in women using COC, DHEA-S after adjustment correlated positively with fasting and stimulated glucose, insulin and C-peptide, and negatively with insulin sensitivity. In this respect, the benefit of DHEA(S) supplementation seems - at least in terms of its alleged antiobesity and antidiabetogenic effects - to be more than controversial., B. Bendlová, J. Vrbíková, M. Hill, M. Vaňková, P. Lukášová, J. Včelák, D. Vejražková, K. Dvořáková, R. Hampl, K. Vondra, L. Stárka., and Obsahuje bibliografii a bibliografické odkazy
Obesity is often associated with metabolic impairments in peripheral tissues. Evidence suggests an excess of free fatty acids (FFA) as one factor linking obesity and related pathological conditions and the impact of FFA overload on skeletal muscle metabolism is described herein. Obesity is associated with dysfunctional adipose tissue unable to buffer the flux of dietary lipids. Resulting increased levels and fluxes of plasma FFA lead to ectopic lipid deposition and lipotoxicity. FFA accumulated in skeletal muscle are associated with insulin resistance and overall cellular dysfunction. Mechanisms supposed to be involved in these conditions include the Randle cycle, intracellular accumulation of lipid metabolites, inflammation and mitochondrial dysfunction or mitochondrial stress. These mechanisms are described and discussed in the view of current experimental evidence with an emphasis on conflicting theories of decreased vs. increased mitochondrial fat oxidation associated with lipid overload. Since different types of FFA may induce diverse metabolic responses in skeletal muscle cells, this review also focuses on cellular mechanisms underlying the different action of saturated and unsaturated FFA., J. Tumova, M. Andel, J. Trnka., and Obsahuje bibliografii
Objective: To examine the impact of family history of diabetes mellitus 2 (DM 2) on insulin sensitivity and secretion in lean women with polycystic ovary syndrome (PCOS). Thirteen healthy women (C), 14 PCOS without family history of DM 2 (FH-) and 8 PCOS with family history of DM 2 (FH+) were examined using euglycemic hyperinsulinemic clamp and an arginine secretion test (insulin and glucagon at fasting glycemia (AIRFG and AGRFG) and at hyperglycemia (AIR14 and AG 14)). FH+ women were more insulin resistant than FH- with lower insulin sensitivity index corrected per lean body mass (p<0.05). They had significantly higher triglycerides (p<0.05) and lower HDL-cholesterol (p<0.05) than C or FH- women. Concerning insulin secretion, AIR FG was increased in FH+ women comparing FH- women (p<0.05). Disposition indices derived from AIRFG or AIR14 and insulin sensitivity index did not differ between FH+ or FH-. Thus, women with PCOS with the concomitant family history of DM 2 have lower insulin sensitivity than healthy control women. Insulin resistance observed in these women with PCOS is compensated by increased insulin secretion., J. Vrbíková, T. Grimmichová, K, Dvořáková, M. Hill, S. Stanická, K. Vondra., and Obsahuje bibliografii a bibliografické odkazy
Previous studies revealed altered levels of the circulating insulin-like growth factor-I (IGF-I) and of its binding protein-3 (IGFBP-3) in subjects with coronary atherosclerosis, metabolic syndrome and premature atherosclerosis. Hyperlipidemia is a powerful risk factor of atherosclerosis. We expected IGF-I and IGFBP-3 alterations in subjects with moderate/severe hyperlipidemia but without any clinical manifestation of atherosclerosis. Total IGF-I and IGFBP-3 were assessed in 56 patients with mixed hyperlipidemia (MHL; cholesterol>6.0 mmol/l, triglycerides>2.0 mmol/l), in 33 patients with isolated hypercholesterolemia (IHC; cholesterol>6.0 mmol/l, triglycerides<2.0 mmol/l), and in 29 healthy controls (cholesterol<6.0 mmol/l, triglycerides<2.0 mmol/l). The molar ratio of IGF-I/IGFBP-3 was used as a measure of free IGF-I. IHC subjects differed from controls by lower total IGF-I (164±60 vs. 209±73 ng/ml, p=0.01) and IGF-I/IGFBP-3 ratio (0.14±0.05 vs. 0.17±0.04, p=0.04). Compared to controls, MHL subjects had lower total IGF-I (153±54 ng/ml, p=0.0002) and IGFBP-3 (2.8±0.6 mg/ml, p<0.0001), but higher IGF-I/IGFBP-3 ratio (0.25±0.06, p<0.0001). Differences remained significant after the adjustment for clinical and biochemical covariates, except for triglycerides. Patients with both IHC and MHL have lower total IGF-I compared to controls. The mechanism is presumably different in IHC and MHL. Because of prominent reduction of IGFBP-3 in patients with MHL, they have reduced total IGF-I despite the actual elevation IGF-I/IGFBP-3 ratio as a surrogate of free IGF-I., J. Malík, T. Štulc, D. Wichterle, V. Melenovský, E. Chytilová, Z. Lacinová, J. Marek, R. Češka., and Obsahuje bibliografii a bibliografické odkazy
The presence of insulin resistance is frequently found in essential hypertension. There are, however, only sparse data with respect to the potential presence of insulin resistance in patients with secondary hypertension. We have therefore undertaken a study to reveal the potential occurrence of insulin resistance in primary hyperaldosteronism (PH). The hyperinsulinemic euglycemic clamp technique together with the evaluation of insulin receptor characteristics were used to study insulin resistance in 12 patients with PH. The measured parameters were compared to normal values in control subjects. We have found a significantly lower glucose disposal rate (M, m mol/kg/min) (18.7± 6 vs. 29.3± 4), decreased tissue insulin sensitivity index (M/I, m mol/kg/min per mU/l x100) (23.7± 9.8 vs. 37.5± 11.6) and also lower metabolic clearance rate of glucose (MCRg, ml/kg/min) (3.8± 1.5 vs. 7.0± 1.1) in patients with primary hyperaldosteronism. The insulin receptor characteristics on erythrocytes did not differ in primary hyperaldosteronism as compared to control healthy subjects. We thus conclude that insulin resistance is also present in secondary forms of hypertension (primary hyperaldosteronism) which indicates the heterogeneity of impaired insulin action in patients with arterial hypertension., J. Widimský Jr., G. Šindelka, T. Haas, M. Prázný, J. Hilgertová, J. Škrha., and Obsahuje bibliografii
Critical illness induces among other events production of proinflammatory cytokines that in turn interfere with insulin signaling cascade and induce insulin resistance on a postreceptor level. Recently, local renin-angiotensin system of adipose tissue has been suggested as a possible contributor to the development of insulin resistance in patients with obesity. The aim of our study was to determine local changes of the renin-angiotensin system of subcutaneous and epicardial adipose tissue during a major cardiac surgery, which may serve as a model of an acute stress potentially affecting endocrine function of adipose tissue. Ten patients undergoing elective cardiac surgery were included into the study. Blood samples and samples of subcutaneous and epicardial adipose tissue were collected at the beginning and at the end of the surgery. Blood glucose, serum insulin and adiponectin levels were measured and mRNA for angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1 receptor were determined in adipose tissue samples using RT PCR. Cardiac surgery significantly increased both insulin and blood glucose levels suggesting the development of insulin resistance, while serum adiponectin levels did not change. Expression of angiotensinogen mRNA significantly increased in epicardial adipose tissue at the end of surgery relative to baseline but remained unchanged in subcutaneous adipose tissue. Fat expression of angiotensin-converting enzyme and type 1 receptor for angiotensin II were not affected by surgery. Our study suggests that increased angiotensinogen production in epicardial adipose tissue may contribute to the development of postoperative insulin resistance., T. Roubíček, M. Dolinková, J. Bláha, D. Haluzíková, L. Bošanská, M. Mráz, J. Křemen, M. Haluzík., and Obsahuje bibliografii a bibliografické odkazy