Adult pancreatic stem and progenitor cells could represent an alternative source of insulin-producing tissue for diabetes treatment. In order to identify these cells, we have focused on the human pancreatic cells expressing cell surface molecule CD133, a marker of adult stem cells. We found that population of human CD133-positive pancreatic cells contains endocrine progenitors expressing neurogenin-3 and cells expressing human telomerase, ABCG2, Oct-3/4, Nanog, and Rex-1, markers of pluripotent stem cells. These cells were able to differentiate into insulin-producing cells in vitro and secreted C-peptide in a glucose-dependent manner. Based on our results, we suppose that the CD133 molecule represents another cell surface marker suitable for identification and isolation of pancreatic endocrine progenitors.
- MeSH
- buněčná diferenciace MeSH
- buněčné kultury MeSH
- C-peptid analýza MeSH
- CD antigeny analýza MeSH
- financování organizované MeSH
- glykoproteiny analýza MeSH
- Langerhansovy ostrůvky cytologie fyziologie MeSH
- lidé MeSH
- magnetismus MeSH
- pankreas cytologie MeSH
- peptidy analýza MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- RNA genetika izolace a purifikace MeSH
- separace buněk metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- abstrakt z konference MeSH
The existence of an adult PSC that may be used in the treatment of diabetes is still a matter of scientific debate as conclusive evidence of such a stem cell in the adult pancreas has not yet been presented. The main reason why putative PSC has not yet been identified is the lack of specific markers that may be used to isolate and purify them. In order to increase the list of potential PSC markers we have focused on the human pancreatic cells that express cell surface receptor CXCR4, a marker of stem cells derived from different adult tissues. Here we report that CXCR4-positive pancreatic cells express markers of pancreatic endocrine progenitors (neurogenin-3, nestin) and markers of pluripotent stem cells (Oct-4, Nanog, ABCG2, CD133, CD117). Upon in vitro differentiation, these cells form ILCC and produce key islet hormones including insulin. Based on our results, we assume that CXCR4 marks pancreatic endocrine progenitors and in combination with other cell surface markers may be used in the attempt to identify and isolate PSC.
- MeSH
- buněčná diferenciace MeSH
- C-peptid metabolismus MeSH
- dospělí MeSH
- fluorescenční protilátková technika MeSH
- glukagon metabolismus MeSH
- inzulin metabolismus MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- pankreas * cytologie MeSH
- proteiny intermediálních filament metabolismus MeSH
- proteiny nervové tkáně metabolismus MeSH
- receptor leukemického inhibičního faktoru - alfa-podjednotka metabolismus MeSH
- receptory CXCR4 genetika metabolismus MeSH
- regulace genové exprese MeSH
- senioři MeSH
- separace buněk * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- antropometrie metody MeSH
- distribuce tělesného tuku MeSH
- interpretace statistických dat MeSH
- lidé MeSH
- průřezové studie MeSH
- reprodukční lékařství metody MeSH
- složení těla genetika MeSH
- tělesná hmotnost fyziologie MeSH
- tloušťka kožní řasy MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
Subclinical inflammation is a risk factor for cardiovascular disease. The mechanisms underlying increased levels of inflammatory markers and their changes in response to weight loss are not fully understood yet. It has been proposed that elevated concentrations of C-reactive protein (CRP) are mediated by cytokines produced in adipose tissue. We investigated the changes in circulating CRP after weight reduction, in relation to parameters relevant to the metabolic syndrome. Forty 25- to 35-year-old obese female volunteers participated in an intervention program of dietary education and supervised physical activity for a period of 9 weeks. Anthropological parameters and biochemical measurements (high-sensitivity CRP [hsCRP], plasma lipoproteins, interleukin 6 [IL-6], adiponectin) were analyzed before and after the intervention. Body mass index decreased by more than 7% from 31.5 +/- 4.1 to 29.1 +/- 3.9. Plasma free fatty acid (FFA) concentrations decreased by 30%, high-density lipoprotein cholesterol increased by 8%, and fasting insulin concentrations decreased by 15%. There were no significant changes in either low-density lipoprotein cholesterol or triacylglycerol concentrations. Subcutaneous and visceral adipose tissue mass decreased by 12% and 18%. High-sensitivity CRP concentrations decreased by 30%; however, mean plasma IL-6 and adiponectin concentrations remained unchanged. In linear regression analysis, the changes in plasma hsCRP concentrations were associated with baseline hsCRP concentration, change in triacylglycerols and FFA concentrations, and in waist circumference. The decrease in hsCRP concentration after weight reduction does not appear to be mediated by decreases in circulating IL-6 or adiponectin concentrations; however, change in hsCRP concentration is related to changes in waist circumference and lipid metabolism, reflected by plasma triacylglycerol and FFA levels.
- MeSH
- adiponektin krev MeSH
- C-reaktivní protein analýza MeSH
- cvičení MeSH
- dieta MeSH
- dospělí MeSH
- financování organizované MeSH
- hmotnostní úbytek MeSH
- interleukin-6 krev MeSH
- lidé MeSH
- lipidy krev MeSH
- obezita terapie MeSH
- tělesné váhy a míry MeSH
- životní styl MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
BACKGROUND: Severe pulmonary hypertension (PH) and increased pulmonary vascular resistance (PVR) are important risk factors that predict early postoperative mortality after orthotopic heart transplantation. The aim of our study was to determine the value of B-type natriuretic peptide (BNP) and big endothelin-1 (big ET1) for prediction of severe PH in heart transplant candidates. METHODS: The study population included 43 potential heart transplant candidates (38 males, mean age 52 +/- 7 years). All underwent repeated right-heart catheterizations (2-5 studies) at an interval of 3-4 months, giving a total of 124 examinations, associated with blood sampling for BNP and big ET1 analysis. Severe PH was defined as the mean pulmonary artery pressure (MPAP) > 40 mmHg. RESULTS: Significantly high PVR (PVR > 3.0 Wood units and TPG > 15 mmHg) was noted on 12 occasions in 10 patients; always in the presence of severe PH. Low BNP levels (<67 pg/ml) ruled out the presence of severe PH with a 100% sensitivity, however, with a low specificity (34%). An increase in plasma BNP > 30 pg/ml (>40% of initial value) in subjects with a previous MPAP< or =40 mmHg detected development of severe PH with a 100% sensitivity and an 80-88% specificity. As a total of 58% of patients presented repeatedly with MPAP< or =40 mmHg, serial BNP testing could reduce the need for hemodynamic studies in this subgroup down to 12-20%. CONCLUSIONS: Serial BNP testing in hemodynamically stable heart transplant candidates with MPAP< or =40 mmHg allows reliable detection of development of severe PH, and may significantly reduce the need for repeated right-heart catheterizations in these patients.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- endotelin-1 krev MeSH
- financování organizované MeSH
- lidé středního věku MeSH
- lidé MeSH
- natriuretický peptid typu B krev MeSH
- plicní hypertenze chirurgie krev patofyziologie MeSH
- plicní tlak v zaklínění MeSH
- prognóza MeSH
- radioimunoanalýza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- srdeční katetrizace MeSH
- stupeň závažnosti nemoci MeSH
- transplantace srdce MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
- Publikační typ
- abstrakt z konference MeSH
AIMS: The aim of this study was to evaluate the effect of acutely induced hyperglycaemia on renal sodium handling and to explore the role of the bradykinin-nitric oxide-cGMP signalling pathway. PATIENTS AND METHODS: We compared 20 Type 1 diabetic (DM1) patients without microalbuminuria with 15 weight-, age-, and sex-matched healthy controls (C). Clearances of para-aminohippuric acid (CPAH), inulin (Cin), lithium, sodium, and urinary nitrite/nitrate (NOx), cGMP and bradykinin excretion rates were measured in two 90-min periods: a glycaemic clamp-induced euglycaemia (5 mmol/l-period I) and hyperglycaemia (12 mmol/l-period II) (Study 1) and during time-controlled euglycaemia (5 mmol/l-period I and 5 mmol/l-period II) to avoid the effects of time and volume load (Study 2). RESULTS: Cin and CPAH were not significantly different during euglycaemia (period I of Study 1) in DM1 and controls, whereas fractional excretion of sodium was decreased in DM1 (1.84 +/- 0.75 vs. 2.36 +/- 0.67%; P < 0.05) due to an increase in fractional distal tubular reabsorption of sodium (94.01 +/- 1.94 vs. 92.24 +/- 2.47%; P < 0.05). A comparison of changes during Study 1 and Study 2 revealed acute hyperglycaemia did not change renal haemodynamics significantly, while fractional distal tubular reabsorption of sodium increased (DM1: P < 0.05; C: P < 0.01) and fractional excretion of sodium decreased (P < 0.01) in both groups. The urinary excretion rates of NOx were comparable during euglycaemia in DM1 and C. While in C, they significantly increased during Study 1 (period I: 382 +/- 217 vs. period II: 515 +/- 254 nmol/min; P < 0.01) and Study 2 (period I: 202.9 +/- 176.8 vs. period II: 297.2 +/- 267.5 nmol/min; P < 0.05) as a consequence of the water load, no changes were found in DM1. The urinary excretion of bradykinin was lower in DM1 compared with C (0.84 +/- 0.68 vs. 1.20 +/- 0.85 micro g/min; P < 0.01) during euglycaemia; it was not affected by hyperglycaemia. There were no significant differences between DM1 and C and in cGMP urinary excretion rates following hyperglycaemia. CONCLUSION: This study demonstrates that DM1 without renal haemodynamic alterations is associated with impaired renal sodium handling. Moreover, we did not find a relationship between the renal excretion rates of vasoactive mediators and sodium handling due to hyperglycaemia.
- MeSH
- absorpce fyziologie MeSH
- bradykinin * moč MeSH
- diabetes mellitus 1. typu * metabolismus moč patofyziologie MeSH
- diuréza fyziologie MeSH
- dospělí MeSH
- glykemický clamp metody MeSH
- guanosinmonofosfát cyklický * moč MeSH
- hemodynamika fyziologie MeSH
- hyperglykemie * metabolismus MeSH
- inzulin analýza MeSH
- krevní glukóza analýza MeSH
- ledviny * metabolismus patofyziologie MeSH
- lidé MeSH
- močení fyziologie MeSH
- oxid dusnatý * metabolismus MeSH
- sodík * metabolismus MeSH
- voda fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH