Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelial dysfunction, a well recognized marker of cardiovascular risk, is an early event in arteriosclerosis process. Diabetes mellitus, hypertension and dyslipidemia, known risk factors for coronary disease have been associated with endothelial dysfunction, which improves after the control of these factors. Statins have additional benefits on endothelial function not related to decreasing cholesterol levels, known as pleiotropic effects. Most recently it has been reported the effect of statins promoting bone marrow-derived mononuclear cells. These cells are positive for CD34 and KDR superficial markers of endothelial cellular lineage, which is consistent with the hypothesis that they constitute the endothelial progenitor cells. Circulating endothelial progenitor cells are involved in the repair process of the endothelium after endothelial-cell injury in myocardial ischemia, angina and other stressful situations. Recent studies have demonstrated an inverse relationship between the EPC count in peripheral blood and risk of developing a cardiovascular event. In addition, circulating EPC correlates with the presence of endothelial dysfunction and could play a role as a surrogate biologic marker in vascular function. The effect of statins on endothelial progenitor cells might contribute to improve endothelial function leading to a decrease in vascular risk, independently of their impact on LDL cholesterol. In this paper, we review the role of statins in EPC mobilization, its effect in endothelial function restoration and the relevance of this finding in cardiovascular risk. We also review future therapeutic implications.
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PMID:The role of endothelial progenitor cells and statins in endothelial function: a review. 1797 88

Increase in endothelial cell sloughing and diminished function of endothelial stem cell progenitors in diabetic subjects are well known phenomena. We hypothesized that transplantation of bone marrow stem cells (BMSCs) including mesenchymal stem cells but not limited to CD34(+) stem cells into type 2 diabetic ob mice would restore insulin sensitivity and glucose tolerance. This approach, when combined with induction of HO-1 (a cytoprotective antioxidant system) in the recipient, would further improve bone marrow function. Sublethally irradiated ob mice received BMSC or CD34(+) stem cells from B129SF2/J mice (genetically related) via i.v. or intra bone marrow-bone marrow transplantation (IBM-BMT) at a dose of 5 x 10(6) cells. CD34(+) i.v. administration to ob mice modestly improved glucose tolerance, whereas BMSC administered by the IBM-BMT significantly increased BMSC function, serum adiponectin and glucose tolerance. Induction of HO-1 in the recipients greatly enhanced the ability of BMSC to prevent diabetes. These findings suggest that transplantation of BMSC-mesenchymal stem cells via IBM-BMT in conjunction with induction of HO-1 can eradicate type 2 diabetes. The beneficial effect of HO-1 induction further suggests that the abnormality in endothelial progenitor cells is due to mesenchymal stem cell-stromal cell disorder exacerbated by oxidative stress and decreases in adiponectin. Thus, transplantation of BMSC using the IBM-BMT strategy in conjunction with HO-1 induction offers a novel approach for the treatment of type 2 diabetes.
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PMID:Bone marrow stem cell transplant into intra-bone cavity prevents type 2 diabetes: role of heme oxygenase-adiponectin. 1824 59

Aging and diabetes are associated with exacerbated expression of adhesion molecules. Given their importance in endothelial dysfunction and their possible involvement in the alteration of glomerular permeability occurring in diabetes, we have evaluated expression of the sialomucin-type adhesion molecule CD34 in renal glomerular cells of normal and diabetic animals at two different ages by colloidal gold immunocytochemistry and immunoblotting. CD34 labeling was mostly assigned to the plasma membranes of glomerular endothelium and mesangial processes. Podocyte membranes were also labeled, but to a lesser degree. Short- and long-term diabetes triggers a substantial increase in immunogold labeling for CD34 in renal tissues compared with young normoglycemic animals. However, the level of labeling in old diabetic and healthy control rats is similar, suggesting that the effect of diabetes and aging on CD34 expression is similar but not synergistic. Western blotting of isolated glomerular fractions corroborated immunocytochemical results. Increased expression of CD34 may reflect its involvement in the pathogenesis of glomerular alterations related to age and diabetes. Alterations present in early diabetes, resembling those occurring with age, strengthen the concept that diabetes is an accelerated form of aging.
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PMID:Glomerular CD34 expression in short- and long-term diabetes. 1831 74

We studied the association between plaque vascularity, timing of neurological and ocular symptoms, and presence of cerebral infarction in the ipsilateral cerebral hemisphere on preoperative computed tomographic (CT) scan. Consecutive patients undergoing carotid endarterectomy for carotid stenosis were included. All patients underwent preoperative noncontrast cerebral CT. Histological sections were obtained from carotid endarterectomy specimens and stained with an endothelial cell marker (CD34). Microvessel counts were performed in CD34-stained sections and verified through computerized image analysis. Associations between microvessel density in carotid atherosclerotic plaques, preoperative ipsilateral CT evidence of cerebral infarction, and timing of ipsilateral neurological and ocular events were assessed. Seventy-three patients underwent carotid endarterectomy, of whom 17 were symptomatic within 30 days of carotid endarterectomy, 11 were asymptomatic, and a further 45 had a preoperative symptom-free interval of 31-540 days (median = 56). Eighteen patients (24.6%) had CT evidence of cerebral infarction. Significantly higher microvessel counts were observed in patients with CT evidence of cerebral infarction in the appropriate hemisphere compared with patients who did not (p = 0.02). There was an inverse relationship between the microvessel density in atherosclerotic lesions and the timing of ischemic neurological events (odds ratio [OR] = 4.63, 95% confidence interval [CI] 2.95-7.28, p < 0.001). This relationship was independent of patient age (OR = 1.03, 95% CI 0.55-1.99, p = 0.70), sex (OR = 1.18, 95% CI 0.47-2.05, p = 0.56), smoking (OR = 1.07, 95% CI 0.54-2.09, p = 0.84), diabetes (OR = 0.90, 95% CI 0.45-1.79, p = 0.76), and hypercholesterolemia (OR = 0.98, 95% CI 0.68-1.11, p = 0.88). This study confirms the relationship between angiogenesis in carotid atherosclerotic lesions and development and chronology of ipsilateral hemispheric neurological events.
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PMID:Angiogenesis in carotid atherosclerotic lesions is associated with timing of ischemic neurological events and presence of computed tomographic cerebral infarction in the ipsilateral cerebral hemisphere. 1834 81

Circulating bone marrow derived immature cells, including CD34-positive (CD34(+)) cells, contribute to maintenance of the vasculature, not only as a pool of endothelial progenitor cells (EPCs), but also as a source of growth/angiogenesis factor. We hypothesized that the thiazolidineone compound pioglitazone could stimulate the circulating CD34(+) cells in diabetic patients. Thirty-four patients with type 2 diabetes received 15-30 mg pioglitazone for 24 weeks. The number of circulating CD34(+) cells significantly increased at 12 and continued this effect for 24 weeks (1.08+/-0.39, 1.34+/-0.34 and 1.32+/-0.28cells/microl at 0, 12 and 24 weeks, respectively). The change of CD34(+) cell levels (DeltaCD34(+) cells) between 0 and 12 weeks was significantly correlated with the change of high sensitive C reactive protein levels (Deltahs-CRP) and change in adiponectin levels (Deltaadiponectin) (r=-0.412, r=0.359, respectively). Our study demonstrated that pioglitazone treatment increased circulating CD34(+) cells, suggesting that this effect may at least partly contribute to the anti-atherosclerotic action of pioglitazone.
Diabetes Res Clin Pract 2008 Sep
PMID:Pioglitazone treatment stimulates circulating CD34-positive cells in type 2 diabetes patients. 1863 63

The major obstacle in using pancreatic islet transplantation to cure type I and some type II diabetes is the shortage of the donors. One of ways to overcome such obstacle is to isolate and clone pancreatic stem cells as "seed cells" and induce their differentiation into functional islets as an abundant transplantation source. In this study, a monoclonal human pancreatic stem cell (mhPSC) line was obtained from abortive fetal pancreatic tissues. Pancreatic tissues were taken from abortive fetus by sterile procedures, and digested into single cells and cell clusters with 0.1% type IV collagenase. Cultured in modified glucose-low DMEM with 10% fetal bovine serum (FBS), these single cells and cell clusters adhered to culture dishes, and then primary epidermal-like pancreatic stem cells started to clone. After digesting with 0.25% trypsin and 0.04% EDTA, fibroblasts and other cells were gradually eliminated and epithelioid pancreatic stem cells were gradually purified during generations. Using clone-ring selection, the mhPSCs were obtained. After addition of 10 ng/mL epidermal growth factor (EGF) in cell culture medium, the mhPSCs quickly grew and formed a gravelstone-like monolayer. Continuously proliferated, a mhPSC line, which was derived from a male abortive fetus of 4 months old, has been passed through 50 generations. More than 1 x 10(9) mhPSCs were cryo-preserved in liquid nitrogen. Karyotype analysis showed that the chromosome set of the mhPSC line was normal diploid. Immunocytochemistry results demonstrated that the mhPSC line was positive for the pdx1, glucagon, nestin and CK19, and negative for the insulin, CD34, CD44 and CD45 protein expression. RT-PCR revealed further that the mhPSCs expressed transcription factors of the pdx1, glucagon, nestin and CK19. Also, in vitro induced with beta-mercaptoethanol, the mhPSCs differentiated into nerve cells that expressed the NF protein. Induced with nicotinamide, the mhPSCs differentiated into functional islet-like clusters, as identified by dithizone staining, which expressed the transcription factor of the insulin and secreted the insulin and C-peptide. Furthermore, the transplantation of mhPSCs-induced pancreatic islets into the subcapsular region of the kidney in streptozotocin-induced diabetic rats could reduce blood glucose levels and prolong the life time.
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PMID:Establishing a human pancreatic stem cell line and transplanting induced pancreatic islets to reverse experimental diabetes in rats. 1872 23

A 62-year-old, obese woman, smoking 10 pack/year was admitted to the National Tuberculosis and Lung Diseases Research Institute to diagnose small, round opacities revealed by routine chest X-ray examination. These lesions had been observed for 5 years. The patient had been treated for psoriasis, hypertension, and insulin-independent diabetes. On admission she was in good condition, complaining of a slight productive cough as well as intermittent osteoarticular pain. Physical examination revealed cutaneous psoriatic lesions, slight edema of the lower limbs, and clubbed fingers. Tuberculin test was positive. Chest Computer Tomography scanning showed partially calcified nodules (up to 1 cm in diameter) located in the middle and base areas of both lungs. No evidence of hilar nor mediastinal lymph node enlargement was seen. Lung specimens displayed intraalveolar and intravascular growth of neoplastic cells. Immunohistochemical expression of Factor VIII, CD31 and CD34 antigens was present. Pulmonary epithelioid haemangioendothelioma was diagnosed. After 6 months of observation, progression of the disease was shown. Interferon alpha treatment was introduced. During the therapy, a slight regression of pulmonary changes was noticed and since then stabilization of the disease was observed.
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PMID:Pulmonary epithelioid haemangioendothelioma--interferon 2-alpha treatment--case report. 1878 34

Our objective was to determine the relationships between levels of different dietary nutrients intake with circulating endothelial progenitor cells (EPC) and vascular endothelial function in type II diabetic patients. We studied the daily dietary nutrients intake, the numbers of circulating CD34(+)/KDR(+) EPC and CD133(+)/KDR(+) EPC and brachial artery flow-mediated dilation (FMD) in 88 diabetic patients without prior cardiovascular diseases and 91 sex- and age-matched controls. Compared with controls, diabetic patients had lower CD133(+)/KDR(+) EPC count (48.3 +/- 5.2 vs. 84.6 +/- 7.6/microL, p < 0.001), CD34(+)/KDR(+) EPC count (311 +/- 41 vs. 412 +/- 36/microL, p = 0.045), and FMD (2.54 +/- 0.37% vs. 5.46 +/- 0.47%, p < 0.001). After adjusted for age, sex, smoking history, body weight, hemoglobin A1c level, total calorie intake, other dietary vitamin intake, use of antihypertensives, and lipid lowering agents, a higher intake of thiamine was significantly associated with a higher level of circulating CD34(+)/KDR(+) EPC (beta = 0.49, p = 0.028) and CD133(+)/KDR(+) EPC (beta = 0.45, p = 0.037) in diabetic patients, but not in controls. Furthermore, an increased intake of thiamine from 1st to 4th quartile in diabetic patients independently predicted an absolute increase in FMD by 1.29% (p = 0.026, relative increase = 63.5%). This study demonstrated that daily thiamine intake was positively correlated with the circulating number of EPCs and FMD in patients with type II diabetes, independent of other dietary nutrients intake.
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PMID:Daily intake of thiamine correlates with the circulating level of endothelial progenitor cells and the endothelial function in patients with type II diabetes. 1892 14

To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin (30 mg/kg). After 8 weeks intervention with perindopril (AE, n=10) or valsartan (AR, n=10), the islet function of the animals was evaluated by intravenous insulin release test (IVIRT). The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor (VEGF) in the islets. The microvessel density (MVD) of islets was detected by counting CD34 positive cells. The hypoxia inducible factor (HIF)-1alpha mRNA expression in the islets was detected by RT-PCR. Compared with normal control group (NC, n=10), the area under the curve for insulin from 0 to 30 min (AUCI(0-30)) of diabetes group (DM, n=8) was decreased by 66.3%; the insulin relative concentration (IRC) of betacell was decreased significantly; the relative content of VEGF was increased obviously [(-4.21+/-0.13) vs (-4.06+/-0.29)]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1alpha mRNA was increased by 1.19 times (all P<0.01). Compared with DM group, the AUCI(0-30) of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1alpha was decreased by 27.2% and 29.0% respectively (all P<0.01 or P<0.05). There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.
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PMID:Effect of renin angiotensin system blockade on the islet microvessel density of diabetic rats and its relationship with islet function. 2003 7

Recent studies indicate that immune-associated aplastic anemia (AA) resembles such autoimmune diseases as insulin-dependent diabetes and chronic autoimmune thyroiditis that belong to organ-specific autoimmune diseases. Many independent investigation groups have successfully isolated the pathopoiesis-associated T cell clone causing hematopoiesis failure with a CD4 phenotype from peripheral blood and bone marrow (BM) in AA patients. In the current study, BM CD4(+) T cells were isolated from AA patients and healthy controls with immunomagnetic beads sorting, and proliferation capability, apoptosis features and the impacts of their secreted cytokines on hematopoiesis stem/progenitor cells were compared between them. By (3)H-TdR method, CD4(+) T cells in AA group presented more enhanced proliferative activity. The stimulation index in control group and AA group was 1.47+/-0.24, and 2.51+/-0.34 respectively (P<0.01). After BM CD4(+) T cells were induced by high concentration of CD3 monoclonal antibody for 18 h, evident apoptosis cells could be seen under the electron microscope in both control group and AA group. Flow cytometry revealed that apoptosis rates in the early and late stages of AA group were significantly higher than in control group (P<0.01). Early-stage apoptosis rate in control and AA groups was (6.85+/-1.48)% and (16.98+/-4.40)%, and late-stage apoptosis rate in control group and AA group was (2.65+/-1.57)% and (7.74+/-0.83)%, respectively (P<0.01). The CFU-GM count in AA group and control group was (74.50+/-9.50)/10(4) cells and (124.25+/-19.80)/10(4) cells respectively under an inverted microscope (P<0.01), and the expression levels of CyclinD3 mRNA and protein in cord blood CD34(+) cells were both down-regulated induced by BM CD4(+) T cell culture supernatant in AA patients. These results indicate that BM CD4(+) T cells of AA patients are likely in an abnormally proliferative, and activated state which can correlate intimately with AA hematopoiesis damage. BM CD4(+) T cells in AA patients can secret some soluble cytokines that can inhibit proliferation of hematopoietic stem cells by suppressing the expression of Cyclin D3, resulting in hematopoiesis failure.
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PMID:Proliferation and apoptosis of bone marrow CD4(+) T cells in patients with aplastic anemia and impacts of the secreted cytokines on hematopoietic stem cells from umbilical cord blood. 2015 53


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