Although the mutations in MC4R gene became known as the most common genetic cause of human obesity, the effect of rs12970134 A/G near MC4R gene on insulin resistance has been described. The aim of this study was to determine the effect of rs12970134 on obesity, hormone levels, and glucose metabolism in a cohort of women varying in glucose tolerance: 850 normoglycemic women, 423 diagnosed with polycystic ovary syndrome (PCOS), 402 gestational diabetics (GDM), and 250 type 2 diabetic (T2D) women. We did not confirm the explicit effect of rs12970134 on obesity. However, the influence of the A-allele on body adiposity index was observed in a cohort of women diagnosed with PCOS. In normoglycemic women, the A-allele carriership was associated with lower fasting levels of glucose, insulin, C-peptide, and index of insulin resistance. Furthermore, higher levels of growth hormone, leptin and SHBG, and lower levels of fT3, testosterone, and androstenedione were recorded in normoglycemic A-allele carriers. In conclusion, the study presents the evidence of the impact of rs12970134 on complex hypothalamic regulations., O. Bradnová, D. Vejražková, M. Vaňková, P. Lukášová, J. Včelák, S. stanická, K. Dvořáková, B. Bendlová., and Obsahuje bibliografii
This review article summarizes the problems of metabolic disorders and nutrition imbalances that often occur in chronic kidney failure (CKF) or following regular dialysis treatment. In this survey, we cover the pathogenesis of these disorders, their clinical consequences, and their association with the most severe complications of chronic kidney failure and dialysis treatment. These complications are primarily at herosclerosis, malnutrition, anemia, hyperparathyroidism, and other serious problems that markedly and negatively affect prognosis and the quality of life of uremic patients. Risk factors for cardiovascular disease are discussed in-depth because cardiovascular disease is the leading cause of death in patients with chronic kidney failure. It is important to pay attention to the development of these complications because early diagnosis and therapy can improve the prognosis for these patients and reduce treatment costs., R. Cibulka, J. Racek., and Obsahuje bibliografii a bibliografické odkazy
b1_Rats with diabetes induced by streptozotocin (STZ) and nicotinamide (NA) are often used in animal studies concerning various aspects of diabetes. In this experimental model, the severity of diabetes is different depending on doses of STZ and NA. Moreover, diabetic changes in rats with STZ-NA-induced diabetes are not fully characte rized. In our present study, metabolic changes and insulin secretion were investigated in rats with diabetes induced by administration of 60 mg of STZ and 90 mg of NA per kg body weight. Four to six weeks after diabetes induction, insulin, glucagon and some metabolic parameters were determined to evaluate the severity of diabetes. Moreover, insulin secretory capacity of pancreatic islets isolated from control and diabetic rats was compared. It was demonstrated that admi nistration of 60 mg of STZ and 90 mg of NA per kg body weight induced relatively mild diabetes, since insulin, glucagon an d other analyzed parameters were only slightly affected in diabetic rats compared with control animals. In vitro studies revealed that insulin secretory response was preserved in pancreatic islets of diabetic rats, however, was lower than in islets of control animals. This effect was observed in the presence of different stimuli. Insulin secretion induced by 6.7 and 16.7 mmol/l glucose was moderately reduced in islets of diabetic rats compared with control islets. In the presence of leucine with glutamine, insulin secretion appeared to be also decreased in islets of rats with STZ-NA-induced diabetes. Insulinotropic action of 6.7 mmol/l glucose with forskolin was also deteriorated in diabetic islets. Moreover, it was demonstrated that at a non-stimulatory glucose, pharmacological depolarization of plasma membrane with a concomit ant activation of protein kinase C evoked significant rise in insulin release in islets of control and diabetic rats., b2_However, in diabetic islets, this effect was attenuated. These results indicate that impairment in insulin secretion in pancreatic islets of rats with mild diabetes induced by STZ and NA result s from both metabolic and nonmetabolic disturbances in these islets., T. Szkudelski, A. Zywert, K. Szkudelska., and Obsahuje bibliografii a bibliografické odkazy
n our study, 213 healthy Czech women aged 20 to 65 years were examined and divided into fully reproductive, premenopausal, menopausal and postmenopausal groups. In all subjects body composition was determined by classical anthropometry and metabolic profile was assessed. A total of 146 subjects completed 3-year longitudinal study. Total and LDL cholesterol increased and ratio HDL/total cholesterol decreased with age (p<0.001), most significantly in menopause. Triacylglycerols increased only up to menopause. HDL had a very slight trend to decrease in menopause and postmenopause. Fasting blood glucose level increased progressively (p<0.001), in postmenopause frequently exceeded normal range. Higher BMI, total fat mass and central fat indices were associated with higher total and LDL cholesterol, triacylglycerols, C-peptide, insulin and fasting blood glucose level (p<0.001; fasting blood glucose level to waist-to-hip ratio: p<0.01) and lower HDL cholesterol (p<0.001). Higher C-peptide and insulin were associated with lower HDL cholesterol and higher triacylglycerols (p<0.001). Fasting glucose correlated with LD L cholesterol (p<0.01). Higher SHBG was associated with higher HDL and lower LDL cholesterol (p<0.001). Hormone replacement treatment was related to lower fasting blood glucose level in postmenopausal women (p<0.01). Oral contraception is suggestive of a positive influence on lipid spectrum by increasing the ratio HDL/total cholesterol. Markers of lipid and carbohydrate metabolism are not only age-related, but they are also related to BMI, total fat mass and central fat indices. Therefore, preventive programs should be focused above all on menopausal women., I. Kosková, R. Petrásek, K. Vondra, M. Dušková, L. Stárka., and Obsahuje bibliografii
The aim of the present study was to examine the role of nutritional status, the metabolic hormone ghrelin and their interrelationships in the control of chicken hormones involved in the regulation of reproduction. For this purpose, we identified the effect of food deprivation, administration of ghrelin 1-18 and their combination on plasma levels of testosterone (T), estradiol (E), arginine-vasotocin (AVT) and growth hormone (GH) as well as the release of these hormo nes by isolated and cultured ovarian fragments. It was observed that food deprivation reduces plasma T and E and increases plasma AVT and GH levels. Food restriction also reduced the amount of E produced by isolated ovaries, but it did not affect the ovarian secretion of T and AVT. No ovarian GH secretion was detected. Ghrelin administered to ad libitum fed chickens did not affect plasma T and E levels, but it did increase plasma GH and AVT concentrations. Moreover, it partially prevented the effect of food deprivation on plasma E and AVT levels, but not on T or GH levels. Ghrelin administration to control birds promoted ovarian T, but not E or AVT release and reduced T and no other hormonal outputs in birds subjected to food restriction. Our results (1) confirmed the ovarian origin of the main plasma T and E and the extra-ovarian origin of the main blood AVT and GH; (2) showed that food deprivation-induced suppression of reproduction may be caused by suppression of T and E and the promotion of AVT and GH re lease; (3) suggest the involvement of ghrelin in control chicken E, AVT and GH output; and (4) indicates that ghrelin can either mimic or modify the effect of the intake of low calories on chicken plasma and ovarian hormones, i.e. it can mediate the effect of metabolic state on hormones involved in the control of reproduction., A. V. Sirotkin, A. H. Harrath, R. Grossmann., and Obsahuje bibliografii
Parameters of branched-chain amino acids (BCAA; leucine, isoleucine and valine) and protein metabolism were evaluated using L-[1-14C]leucine and a-keto[1-14C]isocaproate (KIC) in the whole body and in isolated perfused liver (IPL) of rats fed ad libitum or starved for 3 days. Starvation caused a significant increase in plasma BCAA levels and a decrease in leucine appearance from proteolysis, leucine incorporation into body proteins, leucine oxidation, leucine-oxidized fraction, and leucine clearance. Protein synthesis decreased significantly in skeletal muscle and the liver. There were no significant differences in leucine and KIC oxidation by IPL. In starved animals, a significant increase in net release of BCAA and tyrosine by IPL was observed, while the effect on other amino acids was non-significant. We conclude that the protein-sparing phase of uncomplicated starvation is associated with decreased whole-body proteolysis, protein synthesis, branched-chain amino acid (BCAA) oxidation, and BCAA clearance. The increase in plasma BCAA levels in starved animals results in part from decreased BCAA catabolism, particularly in heart and skeletal muscles, and from a net release of BCAA by the hepatic tissue., M. Holeček, L. Šprongl, I. Tilšer., and Obsahuje bibliografii
The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [3 H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [3 H]-DHEAS to [ 3 H]-androstenedione, [3 H]-testosterone, [3 H]-estrone and [ 3 H]-17β-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E1 S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [3 H]-estrone to [3 H]-17β- estradiol. This is the first demonstration that human platelets are able to import DHEAS and E1 S using the OATP family and to convert DHEAS to active DHEA, and to transform E1 S to 17β- estradiol., A. Garrido ... [et al.]., and Obsahuje seznam literatury
The objective of this study was to assess a possible link between microalbuminuria (MA), a major ri sk factor of the cardiorenal syndrome and the brain natriuretic peptide (BNP), a marker of cardiac hypertrophy. Two kidney-one clip (2K-1C) renovascular hypertension was induced in 24 male Wistar rats (weighing 220-250 g). Rats were randomized into four groups for 8 weeks: Sham, not treated; Bos, treated with bosentan; Cap, treated with captopril; Bos/Cap, treated with both drugs. Blood pressure, plasma BNP and transforming growth factor β1 (TGF-β1) concentrations, microalbuminuria and creatininemia as well as cardiac mass, BNP, α- and β-myosin heavy chain (MHC) gene expression and kidney histology were determined. Following stenosis, Sham rats developed hypertension (p<0.001), an increase in BNP (p<0.05) and TGF-β1 (p<0.005) concentrations, creatinine levels (p<0.001), and urinary albumin (p<0.001). Under drug treatment, decreases in blood pressure (p<0.001), creatinine levels (p<0.05), plasma TGF-β1 (p<0.005) and BNP (p<0.05) concentrations, were co ncomitant with the absence of MA which was significantly correlated with reductions in cardiac mass (p<0.05) and hypertrophy markers (BNP and β-MHC gene expression) (p<0.005) as well as in renal fibrosis. These findings suggest a potential link between microalbuminuria evolution and BNP as well as a possible effect of microalbuminuria-lowering therapy on halting the progression, or even inducing the regression of cardiac hypertrophy., Y. Saliba, E. Chouery, A. Mégarbané, H. Jabbour, N. Farès., and Obsahuje bibliografii
The left and right ventricle originate from distinct parts of the cardiac tube, and several genes are known to be differentially expressed in these compartments. The aims of this study were to determine developmental differences in gene expression between the left and right ventricle, and to assess the effect of altered hemodynamic loading. RNA was extracted from isolated left and right normal chick embryonic ventricles at embryonic day 6, 8, and 10, and from day 8 left atrial ligated hearts with hypoplastic left and dilated right ventricles. cRNA was hybridized to Affymetrix Chicken Genome array according to manufacturer protocols. Microarray analysis identified 302 transcripts that were differentially expressed between the left and right ventricle. Comparative analysis detected 91 genes that were different in left ventricles of ligated hearts compared to age-matched ventricles, while 66 were different in the right ones. A large number of the changes could be interpreted as a delay of normal maturation. The approach described in this study could be used as one of the measures to gauge success of surgical procedures for congenital heart disease and help in determining the optimal time frame for intervention to prevent onset of irreversible changes., E. Krejčí, ... [et al.]., and Obsahuje seznam literatury