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1
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DNA methylation, induced by beta-carotene and arachidonic acid, plays a regulatory role in the pro-angiogenic VEGF-receptor (KDR) gene expression in endothelial cells

100%
Kiec-Wilk B., Razny U., Mathers J. C., Dembinska-Kiec A.
Journal of Physiology and Pharmacology
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2009
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tom 60
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nr 4
49-53
DNA methylation is a potent regulator of gene expression. The influence of beta-carotene (BC) and arachidonic acid (AA) on angiogenesis - a new blood vessel formation, was reported. The tyrosine kinase VEGFR-2 receptor (KDR) activation by vascular endothelial growth factor is one of the main angiogenic mechanisms. This study was aimed to investigate a possible role of CpG island methylation on regulation of the pro-angiogenic KDR gene expression after incubation of human endothelial cells with BC and/or AA. Methods: Human umbilical vein endothelial cells (HUVEC) were incubated with BC (1-10 µM) and/or 3 µM AA for 24 hours. The CpG island methylation was quantified using the COBRA method and restriction enzymes' digestion (NewEngland BioLabs). Intracellular protein concentrations were determined by Western blot analysis using the specific antibodies (Santa Cruz). Results: Incubation with BC and AA, decreased methylation of the KDR promoter region. These results well-correlated with the detected, by qRT-PCR, up-regulation of KDR gene expression by BC (p=0.035) as well as by AA. Incubation with BC (p=0.02) and AA (p=0.0014) increased the KDR protein levels in HUVECs. Conclusion: The changes in CpG island methylation of the KDR the pro-angiogenic gene promoter, represents one of the mechanisms involved in regulation of angiogenic response by BC and AA.
2
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Beta-carotene and arachidonic acid induced DNA methylation and the regulation of pro-chemotactic activity of endothelial cells and its progenitors

100%
Kiec-Wilk B., Polus A., Mikolajczyk M., Mathers J. C.
Journal of Physiology and Pharmacology
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2007
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tom 58
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nr 4
DNA methylation is one of the important mechanisms regulating gene expression. Since beta-carotene (BC) was shown to have pro-chemotactic activity and stimulates expression of pro-angiogenic genes, this study was undertaken to define the possible changes in DNA methylation in endothelial cell and its progenitors in the presence of BC. The culture medium for human umbilical vein endothelial cells (HUVEC) and endothelial progenitor cells (EPC) was supplemented with BC (1 - 10 µM) with the presence of arachidonic acid (AA) (3 µM). Global DNA methylation tended to be lower in both endothelial cell lines, after incubation with BC and AA. HUVEC incubated with AA demonstrated the lowest DNA methylation. The decrease of DNA methylation in EPC, induced by BC, was concentration - dependent. The microarray study revealed, that the angiogenesis and homing – related genes were mostly influenced by BC and AA in investigated cells. Our results indicate that BC and AA-induced DNA hypomethylation in EPC and HUVEC, might be a mechanism which may alter gene expression in endothelial cells what in certain conditions may be connected with the suggested pro-malignant effect of this compounds.
3

The chemotactic activity of beta-carotene in endothelial cell progenitors and HUVEC. The microarray analysis

88%
Polus A., Hartwich J., Kiec-Wilk B., Mikolajczyk M., Dembinska-Kiec A.
Acta Biochimica Polonica
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2007
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tom 54
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nr Supplement 4
4
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Clinical factors affecting the perception of hypoglycemia in type 1 diabetes patients treated with personal insulin pumps

88%
Matejko B., Grzanka M., Kiec-Wilk B., Malecki M. T., Klupa T.
Annals of Agricultural and Environmental Medicine
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2013
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tom 20
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nr 1
Introduction and Objective. The ability to perceive the symptoms of hypoglycemia during the early decrease in plasma glucose concentration may be critical for the safety of T1DM patients treated with intensive insulin therapy, including those treated with continuous subcutaneous insulin infusion (CSII). In the presented observational study an attempt was made to asses clinical factors that might affect subjective awareness of hypoglycemia in CSII-treated T1DM patients, with special attention to factors specific for this mode of treatment. Materials and Methods. For the purpose of the study, data of 110 CSII-treated T1DM patients were collected (78 females and 32 males). The records were analyzed from glucose meters (200-300 measurements/download, depending on meter type) and insulin pumps (total insulin dose, basal/bolus ratio, number of boluses/day, bolus calculator and dual wave/square bolus usage, continuous glucose monitoring data) from the last 3 years. Results. It was found that the level of subjective hypoglycemia perception inversely correlated with the number of hypoglycemic episodes per 100 measurements, age, duration of diabetes, time on insulin pump, and positively correlated with mean glycemia (n = 98; r = 0.22; p = 0.0286). With respect to CSII-related factors, hypoglycemia perception inversely correlated with the percentage of basal insulin (n = 106; r = -0.20; p = 0.0354). In stepwise regression analysis, independent predictors for impaired hypoglycemia perception were: age β = -0.29 (p = 0.023), duration of diabetes β = -0.24 (p = 0.029) and number of the hypoglycemia episodes for 100 measurements β = -0.33 (p = 0.0005). Conclusions. Risk factors for impaired hypoglycemia perception in CSII-treated patients include those identified previously for the general population of T1DM individuals. In addition, the presented results suggest that a higher basal/bolus ratio may lead to impairment of the ability to perceive early symptoms of hypoglycemia.
5
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The selected pathophysiological aspects of PPARs activation

88%
Kiec-Wilk B., Dembinska-Kiec A., Olszanecka A., Bodzioch M., Kawecka-Jaszcz K.
Journal of Physiology and Pharmacology
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2005
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tom 56
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nr 2
Peroxisome proliferator activated receptors (PPARs) belong to a subfamily of transcription nuclear factors. Three isoforms of PPARs have been identified: alpha, ß/ and , encoded by different genes and distributed in various tissues. They play important roles in metabolic processes like regulation of glucose and lipid redistribution. They also have anti-atherogenic, anti-inflammatory as well as anti-hypertensive functions. In hypertension-induced cardiac hypertrophy, both PPARalpha and PPAR activation reveal cardio-protective effect. Despite these beneficial functions, several recent experimental reports point to the possibille unfavorable effects of PPARs activation in lipid metabolism (lipotoxicity) in cardiomyocytes, which can lead to pathologic cardiac hypertrophy in such diseases as diabetes type 2, metabolic syndrome or obesity. This paper reviews evidences and hypotheses about the new pathophysiological aspects of PPARs activation.
6

CpG islands methylation induced by betacarotene and arachidonic acid in human endothelial cells and its progenitors

76%
Kiec-Wilk B., Polus A., Mikolajczyk M., Hartwich J., Mathers J., Dembinska-Kiec A.
Acta Biochimica Polonica
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2007
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tom 54
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nr Supplement 4
7
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The MAPK-dependent regulation of the Jagged/Notch gene expression by VEGF, bFGF or PPAR gamma mediated angiogenesis in HUVEC

76%
Kiec-Wilk B., Grzybowska-Galuszka J., Polus A., Pryjma J., Knapp A., Kristiansen K.
Journal of Physiology and Pharmacology
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2010
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tom 61
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nr 2
The Jagged-Notch signalling, plays a crucial role in cell differentiation. Angiogenesis, is regulated by VEGF, bFGF as well as by the free fatty acid metabolites , which are regulators of transcription factors such as peroxisome proliferation activating receptors (PPARs). The study analyzed the signalling pathways involved in the regulation of Jagged-1/Notch-4 expression in endothelial cells (HUVECs) in response to VEGF, bFGF and PPAR- exogenous activator - ciglitazone. HUVECs were incubated with investigated substances for 24 hours, with or without the presence of the MAP-kinases inhibitors were used. Jagged-1 and Notch-4 gene expression was determined using quantitative Real-Time PCR. The Jagged-1/Notch-4 protein expression was compared by flow cytometry, when the phosphorylation-dependent activation of kinases was estimated by Western-blot method. The opposite effect of VEGF, bFGF, or ciglitazone on the Jagged-1/Notch-4 expression on HUVEC was connected with the different activation of MAPKs. Ciglitazone, activated p38 MAPK pathway and simultaneously inhibited phosphorylation of p42/44 MAPK. The pro-angiogenic: bFGF and VEGF, also activated the p38 MAPK, but they did not attenuate the p42/44 MAPK phosphorylation. Maintaining of the Jagged/Notch interactions by VEGF, when down-regulation by bFGF and ciglitazone, seems to be dependent on the different effect on p38 MAPK and p42/44 MAPK pathway regulation.
8

Beta-carotene, and metabolic effect of fatty acids on the Connexin 43 expression in stressed endothelial cells.

76%
Kiec-Wilk B., Knapp A., Goralska J., Awsiuk M., Sliwa A., Staszel T., Dembinska-Kiec A.
Acta Biologica Cracoviensia. Series Botanica. Supplement
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2011
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tom 53
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nr 1
9
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Content available

Assessment of selected food intake frequency in patients with type 1 diabetes treated with personal insulin pumps

76%
Krzyzowska S., Matejko B., Kiec-Wilk B., Wilk M., Malecki M., Klupa T.
Roczniki Państwowego Zakładu Higieny
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2019
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tom 70
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nr 3
Background. It has been established that in Type 1 Diabetes Mellitus (T1DM), regardless of the insulin therapy model used, diet and proper eating habits are still important in the treatment of the disease. The dietary intervention in these patients is aimed at maintaining proper body weight, obtaining target fasting and post meal blood glucose levels, optimizing lipid profiles. Objective. The aim of the study was to assess dietary habits in a homogeneous group of adults with T1DM treated with personal insulin pumps. Material and methods. The study included 141 adult patients (57% women) with type 1 diabetes treated with personal insulin pumps. The surveyed population was characterized by an average age of 25.8 ± 6.2 years, an average duration of diabetes 13.9 ± 6.9 years, and treatment with a personal pump for 8.2 ± 4.1 years and mean BMI 23.0 ± 2.8 g/m2. All were dwellers of south-eastern Poland. The validated KomPAN questionnaire was used to assess the frequency of consumption of individual food products. Results. The mean percentage of HbA1c in the study group was 7.3% [56 mmol/mol]. The mean total cholesterol level was 4.4 mmol/l, HDL - 1.7 mmol/l, LDL - 2.3 mmol/l and triglycerides - 0.8 mmol/l. In the multivariate regression model, no correlation was found between dietary quality parameters and metabolic compensation measured with HbA1c or lipidogram and the place of residence (village, small town, big city). However, there were differences in the quality of the diet depending on the sex. Women were characterized by higher index of a healthy diet (pHDI-10) (26.3 vs 21.4, p=0.005) and lower index of unhealthy diet (nHDI-14) (13.3 vs 18.6, p <0.001) than men. Conclusions. The results of this study clearly suggest, that despite good metabolic control, patients require more education on the choice of healthy product groups.
10
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Content available

Lack of major impact of implementation of the Advanced Hybrid Closed Loop System in technologically-naïve patients with Type 1 Diabetes mellitus on their food choices or weight - a one year follow-up

76%
Krzyzowska S., Matejko B., Cyranka K., Juza A., Kiec-Wilk B., Klupa T.
Annals of Agricultural and Environmental Medicine
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2023
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tom 30
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nr 3
11
Content available remote

The adipose tissue gene expression in mice with different nitric oxide availability

64%
Razny U., Kiec-Wilk B., Polus A., Wator L., Dyduch G., Partyka L., Bodzioch M., Tomaszewska R., Wybranska I.
Journal of Physiology and Pharmacology
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2010
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tom 61
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nr 5
Mice with the knockout of endothelial nitric oxide synthase (eNOS ko) demonstrate symptoms resembling the human metabolic syndrome. NO has been recently demonstrated to be deeply involved in regulation of not only blood flow and angiogenesis, but also in modulation of mammalian basal energy substrate metabolism. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NOS. The enzyme dimethylarginine dimethylaminohydrolase (DDAH) catabolizes ADMA, what leads to increase of endogenous NO bioavailability. This study was aimed to compare the brown (BAT) and white (WAT) adipose tissue gene expression of age matched mice with decreased (eNOS ko) and increased (overexpressing DDAH) endogenous NO generation. The 19 week old eNOS ko mice demonstrated significantly lower weight, higher circulating glucose, insulin, leptin and cholesterol concentrations. The adiponectin as well as fasting triglyceride concentrations were not significantly altered. Animals with DDAH knock in, presented significantly increased angiogenic activity than eNOS ko mice. The microarray analysis pointed to activation of adipogenesis-related genes in eNOS ko mice in WAT, what was in contrast with the inhibition observed in the DDAH overexpressing mice. The angiogenesis related gene expression was down-regulated in both models in comparison to WT animals. This study support the multipotential role of endogenous NO in maintaining homeostasis of energy substrate catabolism.
12

Mitochondrial function of human preadipocytes may be modulated by antioxidants quercetin and beta carotene, and exogenous free fatty acids

64%
Sliwa A., Goralska J., Awsiuk M., Czech U., Gruca A., Kiec-Wilk B., Knapp A., Dembinska-Kiec A.
Polish Journal of Food and Nutrition Sciences
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2011
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tom 61
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nr Suppl.1
13
Content available remote

Correlation of the -3826A G polymorphism in the promoter of the uncoupling protein 1 gene with obesity and metabolic disorders in obese families from Southern Poland

64%
Kiec-Wilk B., Wybranska I., Malczewska-Malec M., Leszczynska-Golabek I., Partyka L., Niedbal S., Jabrocka A., Dembinska-Kiec A.
Journal of Physiology and Pharmacology
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2002
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tom 53
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nr 3
The aim of the study was to examine the allelic frequency of the -3826A>G mutation of UPC1 in patients with familiar obesity and to investigate putative association of this polymorphism with metabolic disorders. One hundred and eighteen overweight / obese patients participated in the study. The UCP1 polymorphism was determined by RFLP. Glucose, lipid, insulin and leptin levels were measured both during OGTT and OLTT. The majority of patients had a homozygous A/A genotype (51,38%), while 14,68% had a G/G genotype. We found no significant association of the G allele with either BMI or glucose tolerance. Patients with the homozygous G/G genotype had significantly higher fasting levels of TG (p<0.04) and decreased levels of HDL-cholesterol (p=0,004). They also had an increased concentration of FFA and the rise of TG levels during the OLTT compared to controls was significant (p=0,058). In addition, the carriers of the G/G genotype had the lowest insulin levels both during OGTT and OLTT. In our study we have demonstrated that the -3826A>G polymorphism of UCP1 does not play a major role in the development of obesity and/or disturbances of glucose metabolism. However, the increased levels of TG and FFA and decreased levels of HDL observed in carriers of the G allele suggest FFA-induced impairment of the HDL turnover and disturbance of the ß-cell function, both of which are risk factors for endothelial injury.
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