The aim of our study was to evaluate rapid insulin pulses and insulin secretion regularity in fasting state in lean women with polycystic ovary syndrome (PCOS) in comparison to lean healthy women. PCOS (n=8) and controls (n=7) underwent every minute blood sampling for 60 min. Insulin pulsatility was assessed by deconvolution and insulin secretion regularity by approximate entropy methodology. PCOS had higher testosterone (p<0.02), prolactin (p<0.05) and lower sex hormone binding globulin (SHBG) (p<0.0006) levels than controls. Approximate entropy, insulin pulse frequency, mass, amplitude and interpulse interval did not differ between PCOS and controls. PCOS had broader insulin peaks determined by a common half-duration (p<0.07). Burst mass correlated positively with testosterone (p<0.05) and negatively with SHBG (p<0.0004) and common half-duration correlated positively with prolactin (p<0.008) and cortisol levels (p<0.03). Approximate entropy positively correlated with BMI (p<0.04) and prolactin (p<0.03). Lean PCOS patients tended to have broader insulin peaks in comparison to healthy controls. Prolactin, androgens and cortisol might participate in alteration of insulin secretion in PCOS-affected women. Body weight and prolactin levels could influence insulin secretion regularity., T. Grimmichová, J. Vrbíková, P. Matucha, K. Vondra, P. P. Veldhuis, M. L. Johnson., and Obsahuje bibliografii a bibliografické odkazy
Type 1 diabetes mellitus (DM 1A) is an autoimmune disease belonging to the most frequent chronic diseases of the childhood and young adults. DM 1A results from immune-mediated destruction of the insulin-producing beta cells of the pancreas. It is a genetically determined disease and many genes or genetic regions were found to be associated with its induction. In addition to the insulin-dependent diabetes mellitus 1 (IDDM1) gene, which marks the HLA region, and IDDM2 which marks the insulin gene, significant associations of DM 1A to other IDMM genes or genetic regions we reported. We shortly review recent achievements in the field, and the state of current knowledge., D. Kantárová, M. Buc., and Obsahuje bibliografii a bibliografické odkazy
Lipoprotein lipase (LPL) is a key factor determining the clearance of triglycerides from the circulation. The enzyme activity is tissue-specifically regulated by insulin, but it is not clear yet how insulin regulates the total LPL activity in the circulation. To answer such question, we measured LPL activity using the intravenous fat tolerance test (IVFTT) that was carried out 1 h before as well as 2 h and 4 h after oral administration of glucose (75 g) in eleven healthy male volunteers. In control experiments, no glucose was given to the subjects. Glucose administration resulted in an expected increase in plasma glucose and insulin and in a suppression of non-esterified fatty acid concentration. The LPL activity assessed in IVFTT as a k2 rate constant did not change in control experiments and decreased to 78 % and 73 % of baseline values 2 h and 4 h after glucose administration, respectively (p=0.01). Similarly, LPL activity measured in the plasma after intravenous injection of heparin at the end of the experiments was 16 % lower (p<0.05) after glucose administration. In conclusion, LPL activity is already downregulated in vivo 2 h after glucose administration. The results of our study indicate that repeated IVFTT is a promising approach for studying acute changes in LPL activity., E. Jindřichová, S. Kratochvílová, J. Kovář., and Obsahuje bibliografii a bibliografické odkazy
Diabetes mellitus is associated with a variety of cardiovascular complications including impaired cardiac muscle function. The effects of insulin treatment on heart rate, body temperature and physical activity in the alloxan (ALX)-induced diabetic rat were investigated using in vivo biotelemetry techniques. The electrocardiogram, physical activity and body temperature were recorded in vivo with a biotelemetry sy stem for 10 days before ALX treatment, for 20 days following administration of ALX (120 mg/kg) and thereafter, for 15 days whilst rats received daily insulin. Heart rate declined rapi dly after administration of ALX. Pre-ALX heart rate was 321 ± 9 beats per minute, falling to 285 ± 12 beats per minute 15-20 days after ALX and recovering to 331±10 beats per minute 5-10 days after commencement of insulin. Heart rate variabilit y declined and PQ, QRS and QT intervals were prolonged after administration of ALX. Physical activity and body temperature declined after administration of ALX. Pre-ALX body temperature was 37.6 ± 0.1 °C, falling to 37.3 ± 0.1 °C 15-20 days after ALX an d recovering to 37.8±0.1 °C 5-10 days after commencement insulin. ALX-induced diabetes is associated with disturbances in heart rhythm, physical activity and body temperature that are variously affected during insulin treatment., F. C. Howarth ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Elevated levels of insulin have been reported to induce both an arterial vasodilation mediated by nitric oxide (NO), and vasoconstriction mediated by endothelin and reactive oxygen radicals. Metformin, used to control blood glucose levels in type 2 diabetes, has also been shown to cause NO-mediated dilation of conduit arteries. It is possible that these contradictory vascular effects are due to a non-direct action on arteries. Therefore, the direct effect of high levels of insulin and metformin infusion on resistance artery diameter was evaluated. Experiments were carried out on the anesthetized pig; blood flow and pressure were measured in the iliac artery. An adjustable snare was applied to the iliac above the pressure and flow measurement site to induce step decreases (3-4 occlusions at 5 min intervals were performed for each infusion) in blood flow, and hence iliac pressure, and the conductance (Δflow / Δpressure) calculated. Saline, insulin (20 and 40 mUSP/l/min), and metformin (1 μg/ml/min) were infused separately downstream of the adjustable snare and their effect on arterial conductance assessed. Insulin at both infusion rates and metformin caused a significant reduction in peripheral vascular conductance. In conclusion, hyperinsulinemia and metformin infusion constrict resistance arterial vessels in vivo., F. Markos, C. M. Shortt, D. Edge, T. Ruane-O'Hora, M. I. M. Noble., and Obsahuje bibliografii
The presence of insulin resistance is frequently found in essential hypertension. There are, however, only sparse data with respect to the potential presence of insulin resistance in patients with secondary hypertension. We have therefore undertaken a study to reveal the potential occurrence of insulin resistance in primary hyperaldosteronism (PH). The hyperinsulinemic euglycemic clamp technique together with the evaluation of insulin receptor characteristics were used to study insulin resistance in 12 patients with PH. The measured parameters were compared to normal values in control subjects. We have found a significantly lower glucose disposal rate (M, m mol/kg/min) (18.7± 6 vs. 29.3± 4), decreased tissue insulin sensitivity index (M/I, m mol/kg/min per mU/l x100) (23.7± 9.8 vs. 37.5± 11.6) and also lower metabolic clearance rate of glucose (MCRg, ml/kg/min) (3.8± 1.5 vs. 7.0± 1.1) in patients with primary hyperaldosteronism. The insulin receptor characteristics on erythrocytes did not differ in primary hyperaldosteronism as compared to control healthy subjects. We thus conclude that insulin resistance is also present in secondary forms of hypertension (primary hyperaldosteronism) which indicates the heterogeneity of impaired insulin action in patients with arterial hypertension., J. Widimský Jr., G. Šindelka, T. Haas, M. Prázný, J. Hilgertová, J. Škrha., and Obsahuje bibliografii
Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue., Daniela Vejrazkova, Marketa Vankova, Petra Lukasova, Josef Vcelak, Bela Bendlova., and Obsahuje bibliografii
The mechanism of action by which insulin increases phosphatidic acid (PA) and diacylglycerol (DAG) levels was investigated in cultured hepatoma cells (HEPG2). Insulin stimulated phosphatidylcholine (PC) and phosphatidyl-inositol (PI) degradation through the activation of specific phospholipases C (PLC). The DAG increase appears to be biphasic. The early DAG production seems to be due to PI breakdown, probably through phosphatidyl-inositol-3-kinase (PI3K) involvement, whereas the delayed DAG increase is derived directly from the PC-PLC activity. The absence of phospholipase D (PLD) involvement was confirmed by the lack of PC-derived phosphatidylethanol production. Experiments performed in the presence of R59022, an inhibitor of DAG-kinase, indicated that PA release is the result of the DAG-kinase activity on the DAG produced in the early phase of insulin action., R. Novotná, P. de Vito, L. Currado, P. Luly, P. M. Baldini., and Obsahuje bibliografii
V práci shrnujeme zkušenosti s aplikací inzulinu pomocí infuzního dávkovače na jednotce intenzivní metabolické péče (JIMP) jednak u nemocných s dekompenzovaným diabetes mellitus, jednak u nemocných přijatých v sepsi nebo jiném život ohrožujícím stavu interní povahy. Pacienti a výsledky: V průběhu 6 měsíců roku 2005 jsme inzulin pomocí dávkovače podali celkem 50 nemocným. 13 z nich mělo známky ketoacidotického nebo hyperosmolárního selhání v průběhu diabetes mellitus. Všichni tito nemocní byli kompenzováni v průběhu 24 hodin a přeloženi do 48 hodin k další léčbě na standardní oddělení. 37 nemocných bylo přijato v kritickém stavu, jehož příčinou byl u 29 jedinců septický stav, u 8 jiné závažné interní onemocnění. V průběhu hospitalizace na JIMP z nich zemřelo 12 nemocných, 8 v průběhu prvních 3 dnů po přijetí. V uvedené skupině nemocných jsme nezjistili významný vztah mezi věkem, přítomností diabetes mellitus a přidruženou kardiovaskulární morbiditou a úmrtím na JIMP, zatímco mortalita na jednotce významně souvisela s úvodní hodnotou C-reaktivního proteinu v krvi (160 mg/l; 32?352 u zemřelých a 111 mg/l; 15?168 u přeživších nemocných), p < 0,01. Vstupní glykemie se významně nelišila mezi nemocnými, kteří zemřeli a přežili, ale průměrná glykemie ze všech měření na JIMP byla významně vyšší u zemřelých (10,4 mmol/l; 6,2?22,4) ve srovnání s přeživšími nemocnými (7,8 mmol/l; 5,8?16,6), p < 0,01. Doba podávání inzulinu byla významně kratší u zemřelých (3,3 dne; 1?6) ve srovnání s přeživšími (5,2 dne; 3?10) nemocnými, p < 0,01. Hodinová dávka inzulinu se mezi zemřelými (2,8 j/hod; 0,6?8,6) a přeživšími (2,6 j/hod; 0,8?7,6) nemocnými významně nelišila. Ve skupině nemocných s průměrnou glykemií méně než 8 mmol/l a/nebo u těch, kdy většina glykemií byla v rozmezí 4,4?8,0 mmol/l, jsme zjistili tendenci k snížené mortalitě, ale rozdíly nedosáhly statistické významnosti. Významně nižší spotřeba inzulinu byla zjištěna u nemocných s průměrnou glykemií nižší než 8 mmol/l a/nebo u těch, u nichž se většina měřených glykemií pohybovala mezi 4,4?8,0 mmol/l. Hypoglykemie definovaná jako glykemie pod 4,4 mmol/l byla přítomna ve 2 % všech měření, celkem u 11 nemocných a její nález nebyl významně asociován s mortalitou na JIMP. Závěr: Mortalita nemocných přijatých v sepsi nebo s jinými život ohrožující stavy interní povahy byla významně vyšší ve skupině nemocných s vyšší průměrnou glykemií ze všech měření na JIMP. U zemřelých nemocných byla celková doba podávání inzulínu významně kratší, ale průměrná hodinová dávka inzulínu se nelišila ve skupině zemřelých a přeživších., Jiří Charvát, S. Pálová, M. Horáčková, and Lit. 16