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排序方式: 共有85条查询结果,搜索用时 15 毫秒
1.
Netherton SJ Jimmo SL Palmer D Tilley DG Dunkerley HA Raymond DR Russell JC Absher PM Sage EH Vernon RB Maurice DH 《Diabetes》2002,51(4):1194-1200
Cardiovascular diseases represent a significant cause of morbidity and mortality in diabetes. Of the many animal models used in the study of non-insulin-dependent (type 2) diabetes, the JCR:LA-cp rat is unique in that it develops insulin resistance in the presence of obesity and manifests both peripheral and coronary vasculopathies. In this animal model, arterial vascular smooth muscle cells (VSMCs) from homozygous obese (cp/cp) rats, but not from age-matched healthy (+/+ or + /cp, collectively defined +/?) littermates, display an " activated" phenotype in vitro and in vivo and have an elevated level of cAMP phosphodiesterase (PDE) activity. In this report, we confirm that cp/cp rat aortic VSMCs have an elevated level of PDE3 activity and show that only particulate PDE3 (PDE3B) activity is elevated. In marked contrast to results obtained in + /? VSMCs, simultaneous activation of adenylyl cyclase and inhibition of PDE3 activity in cp/cp VSMCs synergistically increased cAMP. Although PDE3 inhibition did not potentiate the antimigratory effects of forskolin on +/? VSMCs, PDE3 inhibition did markedly potentiate the forskolin-induced inhibition of migration of cp/cp-derived VSMCs. Although PDE3 activity was elevated in cp/cp rat aortic VSMCs, levels of expression of cytosolic PDE3 (PDE3A) and PDE3B in +/? and cp/cp VSMCs, as well as activation of these enzymes following activation of the cAMP-protein kinase A signaling cascade, were not different. Our data are consistent with an increased role for PDE3 in regulating cAMP-dependent signaling in cp/cp VSMCs and identify PDE3 as a cellular activity potentially responsible for the phenotype of cp/cp VSMCs. 相似文献
2.
Effects of insulin sensitizers on
plaque vulnerability associated with elevated lipid content in
atheroma in ApoE-knockout mice 总被引:4,自引:0,他引:4
Cefalu WT Wang ZQ Schneider DJ Absher PM Baldor LC Taatjes DJ Sobel BE 《Acta diabetologica》2004,41(1):25-31
Abstract. Acute coronary syndromes are generally precipitated by
rupture of lipid-laden, relatively acellular, vulnerable
atherosclerotic plaques with thin fibrous caps. We investigated
whether a high-fat diet alters insulin sensitivity and whether
insulin sensitizers (troglitazone and rosiglitazone) alter the
composition of otherwise lipidladen atherosclerotic plaques in
mice deficient in apolipoprotein E (ApoE). ApoE-knockout mice
were fed a high-fat (n=30) or standard chow (n=10) diet for two
weeks. Thereafter, those fed the high-fat diet were treated with
troglitazone (n=10), rosiglitazone (n=10) or no drug (n=10) for
16 weeks beginning at 8 weeks of age. Carbohydrate metabolism
was assessed with intraperitoneal glucose tolerance tests and
insulin tolerance tests. Plaque composition was characterised
with confocal laser scanning microscopy. The high-fat diet
induced insulin resistance in the absence of weight gain.
Compared with control animals on the high-fat diet, animals
given troglitazone (400 mg/kg/day) or rosiglitazone (4
mg/kg/day) had significantly less area under the curve (AUC) for
insulin (p<0.05) and
glucose disposal (p<0.05).
Despite significant increases in insulin sensitivity with drug
treatment, no change in HDL-cholesterol and triglyceride levels,
nor reduction in atheroma size or lipid content was noted. Thus,
improvement in insulin resistance induced by a high-fat diet in
this animal model of vasculopathy did not alter plaque
composition. 相似文献
3.
Antonio Juli Francisco Blanco Benjamín Fernndez‐Gutierrez Antonio Gonzlez Juan D. Caete Joan Maym Mercedes Alperi‐Lpez Alex Oliv Hctor Corominas Víctor Martínez‐Taboada Isidoro Gonzlez-lvaro Antonio Fernandez‐Nebro Alba Erra Simn Snchez‐Fernndez Arnald Alonso María Lpez‐Lasanta Raül Tortosa Laia Cod Josep Lluis Gelpi Andrs C. García‐Montero Jaume Bertranpetit Devin Absher Richard M. Myers Jesús Tornero Sara Marsal 《Arthritis \u0026amp; Rheumatology》2016,68(6):1384-1391
4.
Jean M Alameh M De Jesus D Thibault M Lavertu M Darras V Nelea M Buschmann MD Merzouki A 《European journal of pharmaceutical sciences》2012,45(1-2):138-149
Glucagon like peptide 1 (GLP-1), a blood glucose homeostasis modulating incretin, has been proposed for the treatment of type 2 diabetes mellitus (T2DM). However, native GLP-1 pharmacokinetics reveals low bioavailability due to degradation by the ubiquitous dipeptydil peptidase IV (DPP-IV) endoprotease. In this study, the glucosamine-based polymer chitosan was used as a cationic polymer-based in vitro delivery system for GLP-1, DPP-IV resistant GLP-1 analogues and siRNA targeting DPP-IV mRNA. We found chitosans to form spherical nanocomplexes with these nucleic acids, generating two distinct non-overlapping size ranges of 141-283 nm and 68-129 nm for plasmid and siRNA, respectively. The low molecular weight high DDA chitosan 92-10-5 (degree of deacetylation, molecular weight and N:P ratio (DDA-Mn-N:P)) showed the highest plasmid DNA transfection efficiency in HepG2 and Caco-2 cell lines when compared to 80-10-10 and 80-80-5 chitosans. Recombinant native GLP-1 protein levels in media of transfected cells reached 23 ng/L while our DPP-IV resistant analogues resulted in a fivefold increase of GLP-1 protein levels (115 ng/L) relative to native GLP-1, and equivalent to the Lipofectamine positive control. We also found that all chitosan-DPP-IV siRNA nanocomplexes were capable of DPP-IV silencing, with 92-10-5 being significantly more effective in abrogating enzymatic activity of DPP-IV in media of silenced cells, and with no apparent cytotoxicity. These results indicate that specific chitosan formulations may be effectively used for the delivery of plasmid DNA and siRNA in a combination therapy of type 2 diabetes. 相似文献
5.
Silica, a fibrogenic material, enhances the proliferation of human lung fibroblasts. Analysis of filmed time-lapse sequences of dividing cells indicates that cell cycle time (or interdivision time, IDT) is significantly decreased in cells exposed in vitro to pure α-quartz. Migration rates for silica-treated cells were larger than those for control cells, but migration rate was not correlated with IDT. To analyze the IDT data, a computer program was used which carries out a nonparametric analysis of survival data (survival time being the IDT or cell cycle time of a given cell). 相似文献
6.
The proliferative response to beryllium chloride of cells in a population of human lung fibroblasts was quantitatively assessed using time-lapse cinematography. A dose of 0.02 μg Be/ml, known to decrease the growth rate of fibroblasts, affects an estimated 75% of the cells in the population, increasing their interdivision time (IDT) by approximately 5 hr. The differences in mean ln(IDT) between treated and control cells were essentially constant for comparable culture sizes ranging from 25 to 250 cells. There was no correlation between mother and daughter cell IDTs in control or treated culture at any culture size. IDTs of sister pairs were highly correlated in control cultures at selected culture sizes while sister pair IDTs of treated cultures were not. The data suggest that while beryllium alters the IDT of fibroblasts, an effect not related to culture size, any given cell affected by beryllium does not impart effects of the mineral to its progeny. 相似文献
7.
This is the first study of the antithrombin III-heparan sulfate natural anticoagulant pathway in human kidneys. Immunocytochemical experiments were done to demonstrate the pathway on normal renal endothelial cells. Enzymatic studies were done to show that the antithrombin III was anchored to endothelium by molecules of heparan sulfate. Displacement studies were done with glycosaminoglycans to show that the antithrombin III was bound to its glycosaminoglycan anchor via a heparinlike binding site, and replacement studies showed that antithrombin III could be returned to the same endothelial cells from which it was displaced. Immunocytochemical studies of biopsies showed that normally functioning renal allografts manifested the endothelial antithrombin III-heparan sulfate anticoagulant pathway. The pathway was compromised or absent from the microcirculation of biopsies from rejecting or rejected renal allografts, and the diminishment of endothelial ATIII was associated with the presence of fibrin deposition. It is concluded that compromise of the antithrombin III-heparan sulfate natural anticoagulant pathway results in compromised renal function in transplanted kidneys. 相似文献
8.
Time lapse cinematography (TLC) affords a direct approach to the in vitro study of the growth of cell populations. A computer program is described that facilitates TLC studies by simplifying the transfer of data from the film review record to computer files, detecting recording and keypunching errors, calculation and printing statistical summaries, and graphical displays of the clone genealogy. 相似文献
9.
Glomangiopericytoma (GPC) is a rare vascular neoplasm that arises almost exclusively from the nasal cavity or paranasal sinuses. GPC is also called sinonasal-type hemangiopericytoma, although current nomenclature, as well as classification in a group with myopericytomas, better emphasizes the relatively indolent behavior of this tumor. The authors present the FDG PET/CT findings of GPC in a 53-year-old with symptoms of nasal congestion and facial pressure. CT and MRI showed a nasal mass to extend along the sphenoid ridge from the posterior nasal cavity into the posterior nasopharynx. PET showed the mass to have uniformly low-grade FDG hypermetabolism. Pathologic examination of the surgical specimen showed classic features of GPC. 相似文献
10.
Kraja AT Vaidya D Pankow JS Goodarzi MO Assimes TL Kullo IJ Sovio U Mathias RA Sun YV Franceschini N Absher D Li G Zhang Q Feitosa MF Glazer NL Haritunians T Hartikainen AL Knowles JW North KE Iribarren C Kral B Yanek L O'Reilly PF McCarthy MI Jaquish C Couper DJ Chakravarti A Psaty BM Becker LC Province MA Boerwinkle E Quertermous T Palotie L Jarvelin MR Becker DM Kardia SL Rotter JI Chen YD Borecki IB 《Diabetes》2011,60(4):1329-1339
OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ~2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ~9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants. 相似文献