To measure the expression s of fatty acid-bunding proteins in monocytes and adipose tissue in relation to metabolism of fatty acids and selected clinical and biochemical manifestations of insulin resistance in patients with metabolic syndrome. The aim ofthe study is to test the effect of in vivo induced hyperinsulinemia /or angiotensin II blockade on expression of fatty acid binding proteins in human monocytes and adipose tissue in healthy volunteers and patients with metabolic syndrome.

Náplní studie je sledování exprese vazebných bílkovin pro mastné kyseliny v monocytech a viscerálním a podkožním tuku ve vztahu k metabolismu mastných kyselin a vybraným projevům inzulinové rezistence u nemocných s metabolickým syndromem a zdravých osob.Testování vlivu akutní in vivo navozené hyperinzulinémie/nebo blokády AT1 receptorů na expresi genů vazebných bílkovin pro mastné kyseliny v monocytech u nemocných s metabolickým syndromem a zdravých osob.

• MeSH
• hyperinzulinismus MeSH
• inhibitory ACE MeSH
• inzulinová rezistence MeSH
• magnetická rezonanční spektroskopie metody   MeSH
• mastné kyseliny metabolismus   MeSH
• metabolický syndrom MeSH
• monocyty MeSH
• receptor angiotensinu typ 1 MeSH
• tukové buňky metabolismus   MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie
• endokrinologie
• diabetologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

The hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry (IC) is used for estimation of insulin-stimulated substrate utilization. Calculations are based on urinary urea nitrogen excretion (UE), which is influenced by correct urine collection. The aims of our study were to improve the timing of urine collection during the clamp and to test the effect of insulin on UE in patients with type 1 diabetes (DM1; n=11) and healthy subjects (C; n=11). Urine samples were collected (a) over 24 h divided into 3-h periods and (b) before and during two-step clamp (1 and 10 mIU.kg(-1).min(-1); period 1 and period 2) combined with IC. The UE during the clamp was corrected for changes in urea pool size (UEc). There were no significant differences in 24-h UE between C and DM1 and no circadian variation in UE in either group. During the clamp, serum urea decreased significantly in both groups (p<0.01). Therefore, UEc was significantly lower as compared to UE not adjusted for changes in urea pool size both in C (p<0.001) and DM1 (p<0.001). While UE did not change during the clamp, UEc decreased significantly in both groups (p<0.01). UEc during the clamp was significantly higher in DM1 compared to C both in period 1 (p<0.05) and period 2 (p<0.01). The UE over 24 h and UEc during the clamp were statistically different in both C and DM1. We conclude that urine collection performed during the clamp with UE adjusted for changes in urea pool size is the most suitable technique for measuring substrate utilization during the clamp both in DM1 and C. Urine collections during the clamp cannot be replaced either by 24-h sampling (periods I-VII) or by a single 24-h urine collection. Attenuated insulin-induced decrease in UEc in DM1 implicates the impaired insulin effect on proteolysis.

• MeSH
• analýza moči metody   MeSH
• analýza rozptylu MeSH
• časové faktory MeSH
• chemická stimulace MeSH
• diabetes mellitus 1. typu diagnóza   metabolismus   moč   MeSH
• dospělí MeSH
• dusík močoviny v krvi MeSH
• dusík moč   MeSH
• energetický metabolismus fyziologie   MeSH
• glykemický clamp metody   MeSH
• inzulin aplikace a dávkování   MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• močovina moč   MeSH
• nepřímá kalorimetrie MeSH
• odběr biologického vzorku metody   MeSH
• referenční hodnoty MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH

OBJECTIVE: The potential insulin-sensitizing function of angiotensin II type 1 receptor blockade (ARB) with regard to selected adipokines is not fully explained so far. Our study aimed to explore the influence of acute hyperinsulinaemia and acutely induced ARB on resistin and adiponectin concentrations and expressions in healthy subjects. DESIGN AND METHODS: Plasma adipokines were measured: 1) at 0, 30 and 240 min of hyperinsulinaemic (1 mU/kg per min) euglycaemic (5 mmol/l) clamp (HEC), and 2) during HEC after acute ARB (losartan 200 mg; AT-HEC) using the same protocol, in eight healthy subjects. Needle biopsy of abdominal s.c. fat was performed at 0, 30 and 240 min of both clamps to assess the adipokines' expressions. RESULTS: Comparing the glucose disposals of HEC and AT-HEC, no difference in insulin sensitivity was found. Plasma resistin increased equally during HEC and AT-HEC (P < 0.05). The expression of resistin in s.c. fat increased during HEC (P < 0.05), while no significant changes in expression were observed during AT-HEC. Plasma levels of adiponectin did not change during both clamps. Adiponectin expression increased during HEC (P < 0.05), while it did not change during AT-HEC. CONCLUSIONS: In healthy subjects, acute hyperinsulinaemia is associated with an increase in plasma resistin independently of ARB, while plasma adiponectin is not influenced by insulin or ARB. The expressions of both resistin and adiponectin in s.c. adipose tissue are stimulated by acute hyperinsulinaemia, whereas losartan attenuates their insulin-stimulated expressions. This suggests a potential effect of losartanon adipokines' expression.

• MeSH
• adiponektin genetika   krev   metabolismus   MeSH
• blokátory receptorů AT1 pro angiotensin II aplikace a dávkování   MeSH
• dospělí MeSH
• exprese genu účinky léků   MeSH
• financování organizované MeSH
• fixní kombinace léků MeSH
• glykemický clamp MeSH
• hyperinzulinismus chemicky indukované   MeSH
• inzulin aplikace a dávkování   MeSH
• lidé MeSH
• losartan aplikace a dávkování   MeSH
• nitrobřišní tuk metabolismus   účinky léků   MeSH
• receptor angiotensinu typ 1 fyziologie   MeSH
• resistin genetika   krev   metabolismus   MeSH
• zdraví MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• randomizované kontrolované studie MeSH

Insulin resistance affecting skeletal muscle metabolism is present in the prehypertensive state. The aim of our study was to test the hypothesis that blood pressure value is related to skeletal muscle composition, measured by (31)P magnetic resonance (MR) spectroscopy, and to insulin sensitivity in the offspring of hypertensive parents (OH) and healthy controls. Study groups consisted of 10 healthy young lean OH with normal glucose tolerance, confirmed with oral glucose tolerance test, and 13 controls matched for age, sex, and body mass index. Insulin action was estimated as glucose disposal (M), glucose metabolic clearance rate (MCR), and insulin sensitivity index (M/I) during a 10-hour hyperinsulinemic euglycemic clamp. The sum of immunoreactive insulin values from the oral glucose tolerance test was calculated. (31)P MR spectroscopy was performed on a whole-body MR scanner (Siemens Vision, Erlangen, Germany) operating at 1.5 T and equipped with actively shielded gradient coils. There were no differences in common metabolic and anthropometric parameters between OH and controls except for the blood pressure, which was in the range of normal to high-normal level in OH. Mean blood pressure was significantly higher in OH (95.73 +/- 4.39 vs 83.76 +/- 3.95 mm Hg; P < .001). Trend toward insulin resistance was registered in OH with significantly lower M/I (0.74 +/- 0.47 vs 1.42 +/- 0.65 mg x kg(-1) x min(-1) x mIU(-1) x L(-1); P < .05). There were no significant differences in total serum magnesium (sMg) levels between OH and controls, although a positive correlation exists between sMg and insulin sensitivity expressed as M (r = 0.63, P < .01), MCR (r = 0.54, P < .01), and M/I (r = 0.51, P < .05). No differences in signal intensities of phosphocreatine (PCr), phosphomonoesters, phosphodiesters, inorganic phosphates (Pi), adenosine triphosphates (Patp and betaATP), and calculated concentrations of intracellular ionized magnesium (Mgi) and H(+) ions between the groups were detected. Systolic blood pressure correlates positively with PCr/Patp (r = 0.43, P < .05), Pi/Patp (r = 0.413, P < .05), and Pi/betaATP (r = 0.48, P < .05). Diastolic blood pressure correlates positively only with the ratio Pi/betaATP (r = 0.42, P < .05). The sum of immunoreactive insulin values correlates with PCr/betaATP (r = 0.53, P < .01) and with Pi/betaATP (r = 0.6, P < .01). In conclusion, increase in blood pressure and insulin resistance were confirmed in offspring of OH. Insulin sensitivity is related to sMg and the elevation of blood pressure is associated with the activation of energy metabolism in skeletal muscle. The relationship between muscle energetic characteristics and markers of insulin resistance suggests that the alteration of energy metabolism may be present in early stages of metabolic syndrome.

• MeSH
• dospělí MeSH
• financování organizované MeSH
• glykemický clamp MeSH
• hypertenze genetika   patofyziologie   MeSH
• inzulin fyziologie   MeSH
• inzulinová rezistence MeSH
• kosterní svaly metabolismus   MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• lineární modely MeSH
• magnetická rezonanční spektroskopie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• klinické zkoušky MeSH

Hyperglykémie je typickou součástí metabolického syndromu (MS). V patogenezi hyperglykémie hraje nepochybnou roli inzulinová rezistence (IR), která se velmi pravděpodobně uplatňuje při progresivním selhávání β -buněk. IR zvyšuje riziko rozvoje diabetu a riziko rozvoje kardiovaskulárních komplikací. V praxi není třeba míru IR kvantifikovat, cílové hodnoty v léčbě nejsou stanoveny a její přítomnost předpokládáme v případě, že jsou splněna ostatní diagnostická kritéria syndromu. Naproti tomu hyperglykémie je jedním z nezávislých diagnostických kritérií MS. Zahrnuje kategorie poruch glukózové homeostázy (hraniční glykémie nalačno a porucha tolerance glukózy) a diabetes mellitus. Epidemiologické studie průřezového a prospektivního charakteru dokládají, že hyperglykémie je významným samostatným rizikovým faktorem kardiovaskulárních onemocnění, který se uplatňuje u nemocných s diabetem i u osob s poruchou glukózové homeostázy. Významným prediktorem koronárních příhod jsou hodnoty glykovaného hemoglobinu, glykémie nalačno a zejména glykémie postprandiální. Intervenční mortalitní studie sledující vliv terapeutických postupů cílených na normalizaci glykémie jsou méně průkazné ve srovnání s léčbou dyslipidémie a hypertenze. Základem léčby hyperglykémie jsou režimová opatření, farmakologická intervence všech přidružených projevů MS a podávání látek s hypoglykemizujícím účinkem u osob s diabetem. Objektivita volby určitého farmaka (inzulin, deriváty sulfonylurey, metformin, acarbosa , glitazony, glinidy) není v současné době jasně doložena studiemi sledujícími kardiovaskulární mortalitu a riziko mikrovaskulárních komplikací. Z perorálních antidiabetik je u osob s nadváhou a obezitou lékem první volby metformin či acarbosa. Přestože jsou k dispozici studie dokládající snížení incidence diabetu u osob s MS a poruchou glukózové homeostázy při léčbě farmaky, která ovlivňují inzulinovou rezistenci (thiazolidindiony, metformin) či antiobezitiky (orlistat) či dalšími perorálními antidiabetiky (acarbosa), nejsou tyto postupy zatím standardně doporučeny u osob bez manifestního diabetu.

Hyperglycemia is typically associated with the metabolic syndrome (MS). Insulin resistance (IR) likely to be implicated in progressive B cell failure plays an undisputed role in the pathogenesis of hyperglycemia. IR increases risk of diabetes and cardiovascular complications. In practice, the IR level does not need to be quantified, its target values have not been set and its presence is expected when the remaining diagnostic criteria for MS are met. On the other hand, hyperglycemia is one of the independent diagnostic criteria for MS. It includes glucose homeostasis dysregulation (intermediate fasting glycemia and glucose tolerance disorder) and diabetes mellitus. Cross-sectional and prospective epidemiological studies have shown hyperglycemia to be an important independent risk factor for cardiovascular diseases in patients with diabetes and glucose homeostasis dysregulation. The major predictors of coronary events are the levels of glycated hemoglobin, fasting glycemia and, in particular, postprandial glycemia. Interventional mortality studies on efficacy of glycemia control protocols are less conclusive in comparison with those focused on dyslipidemia and hypertension control. The hyperglycemia management is based on compliance with a specific regimen, pharmacological intervention against all MS associated manifestations and prescription of hypoglycemic agents in patients with diabetes. No conclusive studies on cardiovascular mortality and risk of microvascular complications are currently available to support the choice of a particular drug (i.e. insulin, sulfonylurea derivatives, metformin, acarbose, glitazones, and glinides). Metformin and acarbose are the oral antidiabetic agents of choice in overweight patients. Although a reduced incidence of diabetes has been reported in patients with MS and glucose homeostasis dysregulation treated with IR control drugs (thiazolidinediones, metformin) or obesity control drugs (orlistat) or other oral antidiabetic agents (acarbose), none of these protocols has been recommended as a standard in patients without manifest diabetes.

• MeSH
• akarbóza aplikace a dávkování   MeSH
• diabetes mellitus farmakoterapie   MeSH
• finanční podpora výzkumu jako téma MeSH
• hyperglykemie etiologie   farmakoterapie   komplikace   MeSH
• hypoglykemika aplikace a dávkování   klasifikace   MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• metabolický syndrom farmakoterapie   komplikace   MeSH
• metformin aplikace a dávkování   MeSH
• Check Tag
• lidé MeSH

• Publikační typ
• abstrakty MeSH

• MeSH
• diabetes mellitus 1. typu metabolismus   MeSH
• diabetes mellitus 2. typu metabolismus   MeSH
• finanční podpora výzkumu jako téma MeSH
• inzulin sekrece   MeSH
• inzulinová rezistence MeSH
• kosterní svaly metabolismus   MeSH
• lidé MeSH
• mastné kyseliny metabolismus   MeSH
• obezita MeSH
• poruchy metabolismu glukózy MeSH
• postprandiální období MeSH
• Check Tag
• lidé MeSH

• MeSH
• diabetes mellitus 1. typu metabolismus   patofyziologie   MeSH
• diabetes mellitus 2. typu metabolismus   patofyziologie   MeSH
• finanční podpora výzkumu jako téma MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• obezita metabolismus   patofyziologie   MeSH
• peroxidace lipidů MeSH
• Check Tag
• lidé MeSH