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Oxidation of atherogenic low-density lipoproteins (LDL) plays a key role in the pathogenesis of atherosclerosis. Oxidation stress and inflammation are closely interrelated and they can potentiate one another. In the subendothelial space of the arterial intima, monocytes/macrophages become activated and phagocyte oxidized LDL (oxLDL) via scavenger receptors. It has been demonstrated that oxLDL forms complex with plasma β2-glycoprotein I (β2GPI) and becomes autoantigenic triggering synthesis of specific antiphosholipid antibodies. It has been documented that oxLDL/β2GPI in immune complex with IgG autoantibody is internalized by macrophages through the Fc? receptor. Increased levels of oxLDL/β2GPI were first observed in patients with systemic lupus erythematodes (SLE) and antiphospholipid syndrome (APS), further in individuals with coronary heart disease (CHD) and type 2 diabetes mellitus (DM2T). In a prospective study, initial plasma concentrations of oxLDL/β2GPI correlated with the number and severity of cardiovascular events in patients with chronic CHD over a 2-year period.


Diabetes mellitus and obesity are among the major risk factors for cardiovascular diseases, which are the most common cause of mortality among adults in the Czech Republic. Cancer diseases placed second. An increased frequency of cancers was observed in patients with diabetes mellitus and obese subjects. Both units represent an independent risk factor for neoplasia. In the Czech Republic and in the world there is an increasing number of patients with obesity and diabetes, as well as with pancreatic cancer. Although the exact mechanisms of neoplastic transformation are not fully known, there already appears information about the key regulatory steps which in obese result in insulin resistance, glucose metabolism disorders, topical mild chronic inflammation in adipose tissue, formation of oxygen free radicals and alltogether in cell proliferation. The severity and poor prognosis of pancreatic cancer is the reason for an effort to influence these intermediate steps.


Wildova E.,Centrum pro Vyzkum Diabetu | Andel M.,Centrum pro Vyzkum Diabetu
Diabetologie Metabolismus Endokrinologie Vyziva | Year: 2013

Major milk proteins. casein and whey proteins. are high-quality proteins with unique insulinotropic property that do not increase postprandial blood glucose upon administration. It is believed that these proteins increase insulin secretion by both a direct effect of particulary branched chain amino acids on β-cell of islets of Langerhans in pancreas and also by activation of incretin hormones. However, due to a different amino acid profile and digestion, whey proteins achieve higher insulinotropic effect in comparison with casein proteins.


Fontana J.,Centrum pro Vyzkum Diabetu | Cervinkova Z.,Ustav Fyziologie Lekarske Fakulty | Andel M.,Centrum pro Vyzkum Diabetu
Vnitrni Lekarstvi | Year: 2013

Effects of glucagon-like peptide 1 (GLP-1) on liver cells are very intensively studied. In the metabolism of saccharides GLP-1 stimulates synthesis of glycogen and reduces glucose production - thus acting like insulin. In the lipid metabolism it enhances fatty acid oxidation and lipid transport from hepatocytes while reducing de novo lipogenesis - effects more similar to glucagon action. Some studies suggest beneficial effects of GLP-1 on oxidative stress, endoplasmic reticulum stress, production of inflammatory mediators and dysfunction of biliary secretion. Current results suggest that drugs affecting incretin system could be used in the treatment of certain liver diseases (e.g. NAFLD and NASH) in the future. In the following article we mention the known effects of GLP-1 on liver functions and liver metabolism and we point out its possible future therapeutic use in the treatment of liver diseases.


Brunerova L.,Centrum Pro Vyzkum Diabetu | Andel M.,Centrum Pro Vyzkum Diabetu
Vnitrni Lekarstvi | Year: 2014

The review article summarizes the principles of hedonic regulation of food intake which represents the food intake independent on the maintenance of homeostasis. The theory describing hedonic regulation, so called Incentive Salience Theory, comprises three major processes: liking (positive attribution to food stimulus), wanting (motivation to gain it) and learning (identification of these stimuli and distinguishing them from those connected with aversive reaction). Neuronal reward circuits are the anatomical and functional substrates of hedonic regulation. They react to gustatory and olfactory (or visual) stimuli associated with food intake. A food item is preferred in case its consumption is connected with a pleasant feeling thus promoting the behavioural reaction. The probability of this reaction after repetitive exposure to such a stimulus is increased (learned preference). On the contrary, learned aversion after repetitive exposure is connected with avoidance of a food item associated with a negative feeling. Main mediators of hedonic regulation are endocannabinoids, opioids and monoamines (dopamine, serotonin). Dopamine in dorsal striatum via D2 receptors generates food motivation as a key means of survival, however in ventral striatum (nucleus accumbens) is responsible for motivation to food bringing pleasure. Serotonin via its receptors 5-HT1 A a T-HT2C decreases intake of palatable food. It plays a significant role in the pathogenesis of eating disorders, particularly mental anorexia. There, a food restriction represents a kind of automedication to constitutionally pathologically increased serotonin levels. Detailed understanding of processes regulating food intake is a key to new pharmacological interventions in eating disorders.


Andel M.,Centrum pro Vyzkum Diabetu | Skrha P.,Centrum pro Vyzkum Diabetu | Hajer J.,Centrum pro Vyzkum Diabetu | Trnka A.J.,Centrum pro Vyzkum Diabetu
Diabetologie Metabolismus Endokrinologie Vyziva | Year: 2014

Looking from the point of risk of development of cancer are most antidiabetic drugs either neutral or lead to mild increase of the risk. Metformin is the only antidiabetic drug, which in retrospective studies decreased the risk of malignant diseases (OR 0,54-0,70). In the patients treated with metformin were observed also better results of antitumor treatment. Most studies described also lower risk of pancreatic cancer in diabetic patients treated with metformin. There is a description of patients, treated with metformin from the beginning of pancreatic cancer with prognosis of longer survival compared with those, who were not treated with insulin. On contrary, this is not true, when metformin was started in developer stage of pancreatic cancer. The article gives the survey of contemporary knowledge in this field.


Skrha P.,Centrum Pro Vyzkum Diabetu | Andel M.,Centrum Pro Vyzkum Diabetu | Sedo A.,Ustav Biochemie a Experimentalni Onkologie 1
Diabetologie Metabolismus Endokrinologie Vyziva | Year: 2014

Dipeptidyl peptidase-4 inhibitors represent a newer class of antidiabetic drugs, which we use more in type 2 diabetes mellitus treatment. Recenty, there are several new information regarding their effects on immunity. Partial immunosuppression was observed after their administration, maybe due to affecting chemotaxis and T lymphocyte migration. This immunosuppression can be accompanied on the one hand by adverse effects, such as increased frequency of infections, but on the other hand there are some ideas about utilization this knowledge for the treatment of autoimmune diseases.


Gojda J.,Centrum Pro Vyzkum Diabetu | Svanda J.,Centrum Pro Vyzkum Diabetu | Tesinsky P.,Centrum Pro Vyzkum Diabetu | Andel M.,Centrum Pro Vyzkum Diabetu
Diabetologie Metabolismus Endokrinologie Vyziva | Year: 2014

Case of severe persistent hypoglycaemia in non-diabetic patient caused by atypic antipsychotic olanzapine administration is presented in the case report. Hypoglycaemia was associated with endogenous hypersecretion of insulin and cummulative dose of more than 1000mg of intavenous glukose was needed to maintain normoglycaemia. Similar case-reports from literature are presented in discussion and possible mechanisms leading to hypoglycaemia after atypic antipsychotic administrativ are discussed.


Patkova J.,Centrum Pro Vyzkum Diabetu | Trnka J.,Centrum Pro Vyzkum Diabetu | Andel M.,Centrum Pro Vyzkum Diabetu
Diabetologie Metabolismus Endokrinologie Vyziva | Year: 2012

Free fatty acids (FFA) play an important physiological role in the body, however, chronically elevated plasma FFA are associated with various pathophysiological consequences. Elevated FFA concentrations are linked with the onset of peripheral insulin resistance. Skeletal muscle is an important target tissue for the action of FFA. It was shown that the type of FFA is crucial in the determination of their effect, i.e. the length and the degree of saturation of FFA. Detrimental effects of saturated FFA and, on the other hand, positive effects of unsaturated FFA were shown in cell culture experiments but also in animal and human studies. However, the main mechanism by which saturated fatty acids mediate their effects in skeletal muscle have not been fully elucidated. The main candidates include an increase in production of lipid metabolites like ceramide or diacylglycerol, increased oxidative stress and activation of inflammatory pathways. These phenomena can lead to an induction of insulin resistance, mitochondrial dysfunction and cell apoptosis. Understanding of mechanisms by which unsaturated fatty acids prevent these effects is an important step in the development of new intervention strategies and towards a decrease of the prevalence of diseases associated with insulin resistance.


Hrneioova D.,Centrum Pro Vyzkum Diabetu
Diabetologie Metabolismus Endokrinologie Vyziva | Year: 2015

Cobalamin (vitamin B12) belongs to group B vitamins soluble in water; it is an essential human nutrient - acts as a cofactor of two colalamin-dependent enzymes. A deficiency of cobalamin leads to anemia and neuropathy. Its recommended daily requirement for adults is 2-4 μg. Biosynthesis of cobalamin is nowadays restricted to certain bacteria and archaea; industrially is produced by selected and genetically optimized microorganisms, mainly by Propionibacterium shermanii and Pseudomonas denitrificans strains. Some plants and many animals including humans require cobalamin but do not synthetize it. Naturally rich source of cobalamin is food of animal origin: meat, fish, shellfish, milk and dairy products, eggs. In plant foods, substantial amounts of active form of cobalamin were found in certain species of edible algae-Enteromorpha sp. and Porphyra sp. (known as nori), in some eukaryotic microalgae (Chlorella sp.), edible mushrooms (e.g. Shiitake) and tempeh-fermented soya product. However, reliability of this plant sources remains uncertain.

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