Abstract Objectives. Sedentary lifestyle increasingly observed in the population contributes to the incremental incidence of obesity, cardiovascular diseases, mental disorders, type 2 diabetes, hyper-tension, dyslipidemia, and others. Physical inactivity together with an imbalance in caloric intake and expenditure leads to a loss of muscle mass, reduced insulin sensitivity, and accumulation of the visceral fat. Organokines (adipokines, myokines, hepatokines, etc.) serve in the organism for inter-organ communication. However, human studies focused on the exercise-related changes in plasma levels of certain myokines have produced contradictory results. In the present study, we verified a hypothesis that myokine irisin, which is expected to increase in response to physical activity, induces brain-derived neurotrophic factor (BDNF) production and by this way mediates the beneficial effect of exercise on several brain functions. Subjects and Methods. Women (n=27) and men (n=10) aged 44.5±12.0 years, who were sedentary and overweight/obese (men ≥25%, women ≥28% body fat), participated in the study. The effect of an 8-week intensive lifestyle intervention (150 minutes of moderate physical activity per week, diet modification, and reduction of caloric intake) on the selected organokines (irisin, BDNF) in the context of an expected improvement in cardiometabolic status was examined. Results. The 8-week lifestyle intervention resulted in a significant (p<0.05) reduction in body mass index, body fat, blood pressure, insulin resistance, lipid and liver parameters, and irisin levels (p<0.001). However, BDNF increase in the whole group did not reach statistical significance. After the improvement of cardiometabolic parameters, a significant decrease in irisin and increase in BDNF levels were also observed in the subgroup with unsatisfactory (≤5%) body weight reduction. Neither relationship between irisin and BDNF levels, nor effect of age or sex on their levels was observed. Conclusions. We cannot confirm the hypothesis that exercise-induced irisin may increase the BDNF levels, whereas, the organokine levels in the periphery may not completely reflect the processes in the brain compartments. The observed decrease in irisin levels after 8-week intensive lifestyle intervention program, which was in contrary to its supposed mechanisms of action and dynamics, suggests the presence of several yet undiscovered impacts on the secretion of irisin.
Three-sampled oral glucose tolerance test is the most frequently used method for evaluation of impairment of glucose homeostasis in daily clinical practice. The aim of this study was to answer the question if insulin sensitivity indices (ISI) calculated from standard 3-sampled oral glucose tolerance test (3SoGTT) provide adequate information compared to the outcome when calculated from frequently sampled oral glucose tolerance test (FSoGTT).A total of 73 subjects (aged 17-59 years, BMI 17.9-41.8 kg/m2) underwent a standard frequently sampled oral glucose tolerance test (FSoGTT). Selected indices of insulin sensitivity were calculated using plasma glucose and insulin concentrations from FSoGTT and from samples obtained in 0, 60 and 120 min of the oGTT (3SoGTT). Areas under the peripheral concentration curves of insulin and glucose (AUCi, AUCg) from both approaches were compared.Insulin sensitivity calculated from 3SoGTT was significantly higher compared to the sensitivity calculated from FSoGTT expressed as insulin sensitivity indices ISI Cederholm (ISI(Ced)) and ISI Matsuda (ISI(Mat)), p<0.001 and p<0.05, respectively. There was a difference in AUCg between values estimated from 3SoGTT and FSoGTT (p<0.05). These differences nearly disappeared when the BMI groups (normal weight and overweight/obese) were evaluated separately. No differences were found in AUCi and the AUCg:AUCi ratio between two approaches.It might be supposed that on using 3SoGTT the ISI(Mat) provides greater objectivity in assessing insulin sensitivity than ISI(Ced). Although insulin sensitivity is overestimated when calculated from 3SoGTT, the approach is still valuable for identifying subjects with insulin resistance.
Lower levels of dehydroepiandrosterone sulphate (DHEAS) were found in chronic inflammatory diseases such as rheumatoid arthritis (RA), however, mechanisms for this decrease remains unclear. Recently, several genes has been found to be associated with lower DHEAS levels [1].
Objectives
The aim of our study was to analyze frequency of selected single nucleotide polymorphisms (SNPs) known to be associated with low DHEAS in RA patients and their impact on DHEAS levels during disease.
Methods
1034 participants (438 RA, 596 controls) were analyzed for SNPs in genes ZKSCAN5 (rs11761528), SULT2A1 (rs2637125), HHEX (rs2497306) and ARPC1A (rs740160) by real-time PCR genotyping assay. Serum DHEAS concentration was measured in 156 RA patients and 102 healthy controls by ELISA.
Results
RA patients had significantly lower DHEAS than controls (age-adjusted), in female (p<0.001) as well as in male subgroup (p=0.013). The frequency of DHEAS-related SNPs were similar in RA and control groups. In RA female patients linear regression model adjusted for age and glucocorticoid treatment, showed significant effect of risk alleles in SULT2A1 (p<0.05) and HHEX (p<0.05) genes to lowering serum DHEAS levels.
Conclusions
Complex interactions exist between DHEAS-associated genotypes and adrenal androgen hypofunction in RA suggesting a significant contribution to adrenal androgen hypofunction in RA.
References
Zhai G et al. Eight common genetic variants associated with serum DHEAS levels suggest a key role in ageing mechanisms. PLoS Genet. 2011; 7(4):e1002025.
GH deficiency (GHD) in adults is associated with central adiposity, dyslipidemia, and insulin resistance.The objective of the study was to test the hypothesis that GHD might change the spectrum of adipokines and thus influence the adipose tissue and the whole-body metabolic and inflammatory status leading to development of insulin resistance.This was a single-center observational study with a cross-sectional design.Protein arrays were used to characterize adipokines expressed in the sc adipose tissue obtained from young GHD adults and compared with age-, gender-, and body mass index (BMI)-matched group of healthy individuals. All subjects underwent an oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and magnetic resonance imaging examination.Presence of abdominal obesity, enlarged adipocytes, increased circulating high-sensitivity C-reactive protein, impaired glucose tolerance, and decreased insulin action were found in GHD. Changes in adipokine protein expression due to GHD were highly dependent on the obesity phenotype. Lean GHD individuals (BMI approximately 23 kg/m(2)) had decreased protein levels for stem cell factor and epithelial growth factor, indicating a possible defect in adipocyte differentiation and proliferation. Decrease of vascular endothelial growth factor, stromal cell-derived factor, angiopoietin-2, and brain-derived neurotrophic factor advocated for attenuated angiogenesis and neurogenesis. Presence of obesity (BMI approximately 31 kg/m(2)) eliminated these inhibitory effects. However, adipose tissue expansion in GHD individuals was paralleled by an elevation of adipose tissue proinflammatory cytokines (IL-1beta, interferon-gamma) and chemoattractants (interferon-inducible T cell alpha-chemoattractant, monocyte chemotactic protein-2, monocyte chemotactic protein-3, eotaxin).Our data demonstrate that GHD modulates adipokine and cytokine protein expression pattern, which might influence the adipose tissue growth and differentiation and predispose to tissue hypoxia, inflammation, and a defect in the whole-body insulin action.
The main aim of this study was to propose a method to express whole body insulin sensitivity as estimated by a hyperinsulinemic-euglycemic clamp (HEC) as a dimensionless parameter.Two groups of subjects were examined: The first group was comprised of seven healthy lean volunteers with BMI <25 kg/m(2) and a second group comprised of four obese subjects with BMI ≥30 kg/m(2). The dependence between the M/I index expressing the whole body insulin sensitivity, and the dimensionless whole human body effect E as a ratio of the clearance of glucose and the clearance of insulin after their exogenous administration during the last 40 min of the HEC test, was expressed by regression analysis. Unlike an expression of insulin sensitivity/resistance as a function of M taking into account the space corrections or the M/I index, our whole human body effect represents the insulin sensitivity/resistance as a dimensionless number.A linear dependence between the M/I index and the dimensionless effect E with zero intercept and slope at 2.2623 ± 0.157, r = 0.914, and between the M/I index and the effect E recalculated per kg of human body weight with zero intercept and slope at 0.03164 ± 0.00127, r = 0.978, were observed.The high correlation between the M/I index and new effect E in lean and obese volunteers confirms our proposal that the HEC test could be evaluated by a dimensionless parameter which eliminates potential unit mismatches in the expression of clamp results.
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