• MeSH
• Cell Physiological Phenomena MeSH
• Islets of Langerhans MeSH

• Conspectus
• Fyziologie člověka a srovnávací fyziologie
• NML Fields
• endokrinologie

• Conspectus
• Fyziologie člověka a srovnávací fyziologie
• NML Fields
• vnitřní lékařství

• MeSH
• Echocardiography methods   instrumentation   statistics & numerical data   MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Endothelins blood   MeSH
• Research Support as Topic MeSH
• Ventricular Function, Right physiology   MeSH
• Interleukin-6 blood   MeSH
• Catheterization methods   instrumentation   MeSH
• Humans MeSH
• Cardiac Output, Low diagnosis   etiology   ultrasonography   MeSH
• Ultrasonography, Doppler methods   instrumentation   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Comparative Study MeSH

AIM: To study the impact of family history (FH) of type 2 diabetes mellitus on beta-cell compensatory mechanism in women with polycystic ovary syndrome (PCOS). SUBJECTS AND METHODS: A total of 70 women with PCOS, 14 with first-degree relative with type 2 diabetes mellitus (T2DM) (FH+), 56 with negative FH of T2DM (FH-) and 72 age and BMI matched control healthy women (CNT) underwent oral glucose tolerance test (OGTT). Insulin resistance was evaluated as oral glucose index (OGIS); insulin and C-peptide secretion as the insulinogenic index in 30th min of OGTT. RESULTS: Fasting blood glucose levels were significantly higher in FH+ than in FH- (p < 0.05). Fasting insulin was higher in FH+ than in CNT (p < 0.05). Fasting C-peptide was significantly higher in both FH- and FH+ than in CNT (p < 0.05 and p < 0.01, respectively). OGIS was lower in FH+ than in FH- or in CNT (p < 0.05). Insulinogenic index calculated from C-peptide values (II-Cp) was lower in FH+ than in CNT (p < 0.05). Adaptation index calculated from the values of OGIS and insulinogenic index was significantly lower in FH+ than in CNT or in FH- (p < 0.0001 and p < 0.01, respectively). CONCLUSIONS: Insulin resistance and defective early-phase insulin secretion is present only in those PCOS-affected subjects who had positive FH of T2DM.

• MeSH
• Analysis of Variance MeSH
• Insulin-Secreting Cells physiology   metabolism   MeSH
• C-Reactive Protein genetics   metabolism   MeSH
• Diabetes Mellitus, Type 2 genetics   physiopathology   MeSH
• Adult MeSH
• Glucose Tolerance Test MeSH
• Body Mass Index MeSH
• Insulin genetics   metabolism   MeSH
• Insulin Resistance genetics   MeSH
• Blood Glucose genetics   metabolism   MeSH
• Humans MeSH
• Area Under Curve MeSH
• Polycystic Ovary Syndrome genetics   metabolism   physiopathology   MeSH
• Testosterone metabolism   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

V posledních deseti letech došlo k mimořádně bouřlivému rozvoji molekulární biologie a genetiky. Denně přibývají nové poznatky umožněné nejen procesem vlastního výzkumu, ale též obrovským rozvojem jeho technologického zázemí. Uvedený rozvoj výzkumu přiblížil dobu, kdy výsledky výzkumu se stanou součástí praktické medicíny i jiných odvětví. Tak, jako jsme museli znát alespoň základy klasické biochemie, abychom porozuměli základům farmakologie, tak pro blízkou budoucnost bude nezbytné znát minimální základy molekulární biologie a genetiky, abychom byli schopni zodpovědně využívat možností diagnostiky a terapie nemocí, které nám současné výzkumy nabídnou. Proto se autor pokusil shrnout základní a zjednodušené informace o struktuře a funkci receptorů, o přenosu informace (signálu) z extracelulárního prostoru přes membránu do cytosolu a pak dále na úroveň transkripce. Na příkladu desenzitizace beta adrenoreceptoru je pak naznačena šíře složitosti popsaných procesů.

The extraordinary intensive development of the molecular biology and the genetics as well as the technological development supporting both sciences brought an unusual amount of our knowledges that were discovered in the past 10 years. The mentioned results of the research are still the closer part of the practical medicine. The basic knowledge of the molecular biology and the genetics became very important for the everyday medical practice. Therefore the author attempted to summarize and simplify the information about the structure and the function of the receptors and about the transduction of the signals from the extracellular side across the cell membranes to the cytosol and then to the transcriptional level. The example of the desensitization of beta 2-adrenoceptor was used to show the extensive difficulties of the described processes.

• MeSH
• Research Support as Topic MeSH
• Receptors, Cell Surface physiology   classification   MeSH
• Signal Transduction MeSH
• Publication type
• Review MeSH

• MeSH
• Exercise physiology   MeSH
• Hormones, Ectopic metabolism   MeSH
• Endocrinology MeSH
• Research Support as Topic MeSH
• Interleukin-6 metabolism   MeSH
• Intracellular Signaling Peptides and Proteins analysis   metabolism   MeSH
• Leptin analysis   metabolism   MeSH
• Humans MeSH
• Metabolic Syndrome etiology   metabolism   prevention & control   MeSH
• Obesity etiology   MeSH
• Physical Exertion MeSH
• Tumor Necrosis Factor-alpha metabolism   therapeutic use   MeSH
• Adipose Tissue metabolism   MeSH
• Check Tag
• Humans MeSH

Despite the fact that environmental pollution has been implicated in the global rise of diabetes, the research on the impact of emerging pollutants such as novel flame retardants remains limited. In line with the shift towards the use of non-animal approaches in toxicological testing, this study aimed to investigate the effects of two novel flame retardants tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPhP) in rat (INS1E) and human (NES2Y) pancreatic beta-cell lines. One-week exposure to 1 μM and 10 μM TDCIPP and TPhP altered intracellular insulin and proinsulin levels, but not the levels of secreted insulin (despite the presence of a statistically insignificant trend). The exposures also altered the protein expression of several factors involved in beta-cell metabolic pathways and signaling, including ATP citrate lyase, isocitrate dehydrogenase 1, perilipins, glucose transporters, ER stress-related factors, and antioxidant enzymes. This study has brought new and valuable insights into the toxicity of TDCIPP and TPhP on beta-cell function and revealed alterations that might impact insulin secretion after more extended exposure. It also adds to the scarce studies using in vitro pancreatic beta-cells models in toxicological testing, thereby promoting the development of non-animal testing strategy for identifying pro-diabetic effects of chemical pollutants.

• MeSH
• Insulin-Secreting Cells * drug effects   metabolism   MeSH
• Cell Line MeSH
• Homeostasis * drug effects   MeSH
• Insulin * metabolism   MeSH
• Rats MeSH
• Humans MeSH
• Organophosphates toxicity   MeSH
• Organophosphorus Compounds * toxicity   MeSH
• Proinsulin metabolism   MeSH
• Flame Retardants * toxicity   MeSH
• Insulin Secretion drug effects   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Corpus Luteum anatomy & histology   drug effects   secretion   MeSH
• Follicle Stimulating Hormone physiology   MeSH
• Cells, Cultured MeSH
• Ovarian Follicle physiology   MeSH
• Progesterone secretion   MeSH
• In Vitro Techniques MeSH
• Animals MeSH
• Check Tag
• Animals MeSH

Diabetes mellitus 2. typu (DM2) je heterogenní onemocnění, na jehož rozvoji se podílejí genetické faktory i vnější prostředí. Přes značné úsilí, které je mapování genetického pozadí DM2 věnováno, nejsou genetické příčiny nejběžnějších forem diabetu objasněny. V posledních letech je v souvislosti s DM2 věnována velká pozornost draselným kanálům pankreatických beta buněk, neboť hrají stěžejní úlohu v regulaci inzulinové sekrece. Článek shrnuje poznatky o struktuře a funkci draselných kanálů se zaměřením na jejich zapojení do etiopatogeneze DM2. Zvláštní pozornost je věnována polymorfismu E23K, který je považován za jeden z nejvýznamnějších genetických rizikových faktorů,které byly v souvislosti s DM2 dosud odhaleny.

Type 2 diabetes mellitus (DM2) is generally perceived as a heterogeneous polygenic disorder influenced by both hereditary and environmental factors. Despite intensive investigations, little progress has been made in identifying genes that impart susceptibility to the common late-onset forms of the disease. Recently, genes encoding for components of ATP-sensitive K+ channels in pancreatic beta cells have been widely considered as DM2 targets. These channels control insulin secretion by coupling metabolism to membrane electrical activity. The article summarizes knowledge concerning structure and function of the channels with respect to DM2. A common E23K polymorphism in the pore-forming subunit of the channels, which belongs to the most important genetic risk factors for DM2 yet identified, is discussed here.

• MeSH
• Diabetes Mellitus, Type 2 etiology   genetics   MeSH
• Potassium Channels physiology   genetics   chemistry   MeSH
• Research Support as Topic MeSH
• Genes genetics   MeSH
• Langerhans Cells pathology   secretion   MeSH
• Humans MeSH
• Mutation MeSH
• Polymorphism, Genetic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Comparative Study MeSH

Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients' cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.

• MeSH
• Insulin-Secreting Cells metabolism   MeSH
• Diabetes Mellitus, Type 1 genetics   metabolism   pathology   MeSH
• Diabetes Mellitus, Type 2 genetics   metabolism   pathology   MeSH
• Adult MeSH
• Homeostasis genetics   MeSH
• Insulin-Like Growth Factor Binding Protein 3 genetics   metabolism   MeSH
• Immunoblotting MeSH
• Cells, Cultured MeSH
• Middle Aged MeSH
• Humans MeSH
• Membrane Proteins genetics   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice, Inbred NOD MeSH
• Mice, Knockout MeSH
• Mice, Transgenic MeSH
• Reverse Transcriptase Polymerase Chain Reaction MeSH
• Gene Expression Regulation * MeSH
• Signal Transduction genetics   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH