• MeSH
• diabetes mellitus 1. typu terapie   MeSH
• inzulin terapeutické užití   MeSH
• péče o sebe MeSH
• vzdělávání pacientů jako téma MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• vnitřní lékařství

Ticks are blood-feeding arachnids transmitting a variety of pathogens to humans and animals. A unique trait in tick physiology is their ability to engorge and digest large amounts of host blood, ensuring their high reproductive potential. Activation of the blood digestive machinery in the tick gut, as well as processes controlling maturation of ovaries, are triggered upon blood meal uptake by still largely unknown mechanisms. Sensing of the nutritional status in metazoan organisms is facilitated by the evolutionarily conserved Insulin Signaling Pathway (ISP) and the interlinked Target of Rapamycin (TOR) pathway. Recently, we have identified three components of these pathways in the hard tick Ixodes ricinus midgut transcriptome, namely a putative insulin receptor (InR), and the downstream intracellular serine/threonine kinases AKT and TOR. In this study, we primarily focus on the molecular and functional characterization of the I. ricinus insulin receptor (IrInR), the first InR characterized in Chelicerates. A phylogenetic analysis across the major Arthropod lineages demonstrated that ticks possess only one gene encoding an InR-related molecule. Tissue expression profiling by quantitative PCR in semi-engorged I. ricinus females revealed that the IrInR, as well as AKT (IrAKT) and TOR (IrTOR) are expressed in various organs, with the highest expression being detected in ovaries. We have further evaluated the impact of RNAi-mediated knock-down (KD) of IrInR, IrAKT, and IrTOR on tick blood-feeding and reproductive capacity. Weights of engorged IrInR KD females and laid egg clutches were reduced compared to the control group, and these quantitative parameters clearly correlated with the efficiency of RNAi-KD achieved in individual ticks. The most striking phenotype was observed for IrAKT KD that impaired tick feeding and completely aborted egg production. A recombinant extracellular fragment of the IrInR α-subunit was used to produce antibodies in experimental rabbits to assess its potential as a protective antigen against tick feeding and reproduction. Our data clearly indicate the functionality of the ISP in ticks and demonstrate the need for further investigation of specific roles played by the endogenous insulin-like peptides in tick physiological processes.

• MeSH
• inzulin genetika   metabolismus   MeSH
• klíště genetika   metabolismus   MeSH
• proteiny členovců analýza   MeSH
• receptor inzulinu analýza   MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• fibroblasty fyziologie   MeSH
• inzulin MeSH
• lidé MeSH
• nanismus MeSH
• receptory buněčného povrchu fyziologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• buněčné linie MeSH
• DNA MeSH
• inzulin MeSH
• křečci praví MeSH
• somatomediny MeSH
• techniky in vitro MeSH
• transformace genetická MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• zvířata MeSH

• MeSH
• dimerizace MeSH
• fenylalanin metabolismus   MeSH
• finanční podpora výzkumu jako téma MeSH
• insulinu podobný růstový faktor I genetika   chemie   metabolismus   MeSH
• inzulin genetika   chemie   metabolismus   MeSH
• lidé MeSH
• metylace MeSH
• molekulární modely MeSH
• prasata MeSH
• tyrosin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH

The insulin gene mutation c.137G>A (R46Q), which changes an arginine at the B22 position of the mature hormone to glutamine, causes the monogenic diabetes variant maturity-onset diabetes of the young (MODY). In MODY patients, this mutation is heterozygous, and both mutant and wild-type (WT) human insulin are produced simultaneously. However, the patients often depend on administration of exogenous insulin. In this study, we chemically synthesized the MODY mutant [GlnB22]-insulin and characterized its biological and structural properties. The chemical synthesis of this insulin analogue revealed that its folding ability is severely impaired. In vitro and in vivo tests showed that its binding affinity and biological activity are reduced (both approximately 20% that of human insulin). Comparison of the solution structure of [GlnB22]-insulin with the solution structure of native human insulin revealed that the most significant structural effect of the mutation is distortion of the B20-B23 β-turn, leading to liberation of the B chain C-terminus from the protein core. The distortion of the B20-B23 β-turn is caused by the extended conformational freedom of the GlnB22 side chain, which is no longer anchored in a hydrogen bonding network like the native ArgB22. The partially disordered [GlnB22]-insulin structure appears to be one reason for the reduced binding potency of this mutant and may also be responsible for its low folding efficiency in vivo. The altered orientation and flexibility of the B20-B23 β-turn may interfere with the formation of disulfide bonds in proinsulin bearing the R46Q (GlnB22) mutation. This may also have a negative effect on the WT proinsulin simultaneously biosynthesized in β-cells and therefore play a major role in the development of MODY in patients producing [GlnB22]-insulin.

• MeSH
• diabetes mellitus 2. typu farmakoterapie   genetika   metabolismus   MeSH
• glutamin genetika   MeSH
• inzulin chemie   genetika   metabolismus   terapeutické užití   MeSH
• inzulinová rezistence MeSH
• kultivované buňky MeSH
• lidé MeSH
• missense mutace * MeSH
• molekulární sekvence - údaje MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• sekvence aminokyselin MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• C-peptid MeSH
• hypofyzární hormony MeSH
• konformace proteinů MeSH
• magnetická rezonanční tomografie MeSH

BACKGROUND: Functional electrical stimulation-assisted cycle ergometry (FESCE) can deliver active exercise to critically ill patients, including those who are sedated. Aerobic exercise is known to stimulate skeletal muscle glucose uptake. We asked whether FESCE can reduce intravenous insulin requirements and improve insulin sensitivity in intensive care unit (ICU) patients. METHOD: We performed an a priori-planned secondary analysis of data from an outcome-based randomized controlled trial (NCT02864745) of FESCE-based early-mobility program vs standard of care in mechanically ventilated patients. We analyzed glucose profile, glucose intake, and insulin requirements during ICU stay in all enrolled patients. In a nested subgroup, we performed hyperinsulinemic (120 mIU/min/m2 ) euglycemic clamps at days 0, 7, and 180 (n = 30, 23, and 11, respectively). RESULTS: We randomized 150 patients 1:1 to receive intervention or standard of care. Seventeen (23%) patients in each study arm had a history of diabetes. During ICU stay, patients received 137 ± 65 and 137 ± 88 g/day carbohydrate (P = .97), and 31 vs 35 (P = .62) of them required insulin infusion to maintain blood glucose 8.61 ± 2.82 vs 8.73 ± 2.67 mM (P = .75, n = 11,254). In those treated with insulin, median daily dose was 53 IU (interquartile range [IQR], 25-95) vs 62 IU (IQR, 26-96) in the intervention and control arm, respectively (P = .44). In the subgroup of patients undergoing hyperglycemic clamps, insulin sensitivities improved similarly and significantly from acute and protracted critical illness to 6 months after discharge. CONCLUSION: The FESCE-based early-mobility program does not significantly reduce insulin requirements in critically ill patients on mechanical ventilation.

• MeSH
• elektrická stimulace MeSH
• ergometrie MeSH
• inzulin MeSH
• jednotky intenzivní péče * MeSH
• kritický stav * MeSH
• lidé MeSH
• následné studie MeSH
• umělé dýchání MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Cystic fibrosis related diabetes (CFRD) is an insulinopenic condition. We aimed to detect insulinopenia early and to evaluate the impact of low dose insulin on nutritional status and forced expiratory volume in first second (FEV1). Out of 142 cystic fibrosis patients (CFpts) older than 10 years, 28 with abnormal oral glucose tolerance test in spite of normal fasting glycemia were found to have decreased first phase insulin release and started low dose insulin therapy (median age 15.4 years). Sex and age matched CFpts with normal glucose tolerance (NGT) were observed for comparison. Whereas nutritional status improved following 3 years of insulin administration, FEV1 stabilized in insulin-treated insulinopenic subjects (73.8 +/- 4.3% vs. 73.5 +/- 4.4%), but decreased in the parallel group with NGT who remained without insulin treatment (71.1 +/- 3.8% vs. 61.0 +/- 4.0%; p = 0.001). We conclude that low dose insulin improves nutritional status and stabilizes pulmonary functions. Regular estimation of stimulated insulin secretion in CFpts may allow optimizing treatment.

• MeSH
• časná diagnóza MeSH
• časové faktory MeSH
• cystická fibróza komplikace   MeSH
• dítě MeSH
• glukózový toleranční test MeSH
• glykovaný hemoglobin analýza   MeSH
• hypoglykemika aplikace a dávkování   terapeutické užití   MeSH
• inzulinová rezistence MeSH
• kohortové studie MeSH
• krevní glukóza analýza   MeSH
• lidé MeSH
• následné studie MeSH
• NPH inzulin aplikace a dávkování   terapeutické užití   MeSH
• plíce účinky léků   patofyziologie   MeSH
• porucha glukózové tolerance krev   komplikace   farmakoterapie   patofyziologie   MeSH
• prediabetes krev   komplikace   farmakoterapie   patofyziologie   MeSH
• prospektivní studie MeSH
• respirační funkční testy MeSH
• studie případů a kontrol MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS/HYPOTHESIS: The aim of this study was to investigate whether dynamic strength training modifies the control of lipolysis, with particular attention paid to the involvement of the antilipolytic adrenergic alpha 2A receptor (ADRA2A) pathway. METHODS: Twelve obese men (age: 47.4+/-2.8 years; BMI: 32.7+/-0.9) were investigated during a 210-min euglycaemic-hyperinsulinaemic clamp conducted before and after 3 months of dynamic strength training. Before and during the third hour of the clamp, the lipolytic effect of a perfusion of isoproterenol or adrenaline (epinephrine) alone or associated with the ADRA2A antagonist phentolamine was evaluated using the microdialysis method of measuring extracellular glycerol concentration (EGC) in subcutaneous abdominal adipose tissue (SCAAT). In addition, biopsies of SCAAT were carried out before and after training to determine mRNA levels RESULTS: The training increased insulin sensitivity in adipose tissue. The decrease of EGC was more pronounced during the clamp conducted after the training period than during the clamp done in pre-training conditions. Before and after the training, catecholamines induced an increase in EGC, the increase being lower during the clamp on each occasion. The isoproterenol-induced increase in EGC was higher after the training. Adrenaline-induced lipolysis was potentiated by phentolamine after but not before the training. There were no training-induced changes in mRNA levels of key genes of the lipolytic pathway in SCAAT. CONCLUSIONS/INTERPRETATION: In obese subjects, dynamic strength training improves whole-body and adipose tissue insulin responsiveness. It increases responsiveness to the adrenergic beta receptor stimulation of lipolysis and to the antilipolytic action of catecholamines mediated by ADRA2As.

• MeSH
• adrenalin fyziologie   MeSH
• alfa-2-adrenergní receptory - antagonisté MeSH
• alfa-2-adrenergní receptory genetika   metabolismus   MeSH
• antagonisté beta-2-adrenergních receptorů MeSH
• beta-2-adrenergní receptory genetika   metabolismus   MeSH
• cyklické nukleotidfosfodiesterasy, typ 3 MeSH
• dospělí MeSH
• fentolamin farmakologie   MeSH
• financování organizované MeSH
• glycerol analýza   chemie   MeSH
• glykemický clamp MeSH
• inzulin fyziologie   MeSH
• inzulinová rezistence fyziologie   MeSH
• isoprenalin farmakologie   MeSH
• kyseliny mastné neesterifikované krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipolýza MeSH
• messenger RNA analýza   MeSH
• metabolismus lipidů MeSH
• obezita metabolismus   patofyziologie   MeSH
• podkožní břišní tuk chemie   metabolismus   MeSH
• sterolesterasa fyziologie   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• klinické zkoušky MeSH