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
To test the hypothesis that neonatal GLP-1 exposure may program myosin heavy chain (MyHC) composition in adult skeletal muscle, two-day-old rats were transfected intramuscularly with vacant vector plasmid (VP), or recombinant plasmid expressing secretory GLP-1 at the doses of 60 μg (LG) and 120 μg (HG), respectively. Expression of GLP-1 mRNA was detected in muscles of both LG and HG rats 7 days after transfection, with more abundant GLP-1 transcript seen in LG rats. In accordance with the GLP-1 expression, LG rats demonstrated more significant responses to neonatal GLP-1 exposure. Small yet significant growth retardation was observed in LG rats, which is accompanied with significantly reduced serum insulin concentration at 8 weeks of age compared to VP rats. The responses of skeletal muscle were dependent on muscle type. Significant increase of PGC-1α and GLUT4 mRNA expression was detected in soleus of LG rats, whereas a MyHC type switch from ⅡB to Ⅰ was seen in gastrocnemius. These results indicate that neonatal exposure of healthy pups to ectopic GLP-1 causes growth retardation with decreased serum insulin as well as muscle type-dependent modifications in MyHC type composition and metabolic gene expression in adult rats., L. Wang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The impact of anesthetic agen ts on endocrine and metabolic factors is an important issue. The present study has compared the effects of a short-term exposure to diethyl ether, isoflurane, or CO2 on plasma corticosterone, insulin and glucose concentrations since the duration of anesthetic exposure may have an effect on those factors. Male rats were divided into fed and fasted groups. The experimental rats were briefly exposed to diethyl ether, isoflurane, or CO2 (the degree of anesthesia was identical), while a control group was not exposed to the anesthetics. In the fed rats, diethyl ether exposure increased the levels of plasma glucose. CO2 exposure decreased plasma corticosterone and increased plasma glucose levels. Isoflurane exposure caused no changes in plasma corticosterone, glucose, or insulin levels. In the fasted rats, diethyl ether exposure increased plasma corticosterone and reduced plasma insulin levels. The plasma corticosterone and insulin levels were significantly increased by CO2 exposure. Isoflurane exposure decreased plasma insulin levels. A brief exposure to either diethyl ether or CO2 changed the plasma corticosterone, glucose, and insulin levels in fed and/or fasted rats. However, isoflurane exposure had the least effect on the concentration of these factors in both the fed and fasted states., H. Zardooz, F. Rostamkhani, J. Zaringhalam, F. Faraji Shahrivar., and Obsahuje bibliografii