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)

Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells (DC) for the induction of peripheral tolerance may be highly relevant. We examined the properties of DC associated with immune suppression in NOD mice by insulin injection subcutaneously and the ability of which to suppress diabetes transfer by diabetogenic effector cells in secondary NOD-SCID recipients. Our data showed that the surface expressions of MHC II and CD86 on NOD-derived DC were increased after insulin treatment compared with those on PBS controlled mice. The dendritic cells with a mature phenotype and increased MLR stimulation adoptively transferred immune tolerogenic effects in secondary NOD-SCID mice, which were associated with significant greater IL-10, TGF-beta production and CD4(+)CD25(+)T differentiation from splenocytes compared with NOD-SCID control recipients. Moreover, treatment with DC remarkably decreased the incidence of diabetes in secondary recipients. These results suggest that a subtype of DC generated by insulin subcutaneous treated NOD mice confers potential protection from diabetes through polarizing the immune response towards a Th2 regulatory pathway.
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PMID:Insulin administration confers diabetes-preventive properties to NOD mice derived dendritic cells. 1807 57

The effects of hyperglycemia, altered cell function, or inflammatory mediators on implant corrosion are not well studied; yet, these effects are critical to implant biocompatibility and osseointegration. Because implant placement is burgeoning, patients with medically compromising systemic conditions such as diabetes are increasingly receiving implants, and the role of other inflammatory diseases on implant corrosion also needs investigation. In the current study, the corrosion properties of commercially available, machined titanium implants were studied in blood, cultures of monocytic cells, and solutions containing elevated dextrose concentrations. Implant corrosion was estimated by open circuit potentials, linear polarization resistance, and electrical impedance spectroscopy (EIS) for 26 h. In selected samples, THP1 monocytic cells were activated for 2 h with Lipopolysaccharide prior to implant exposure, and IL-1beta secretion was measured to assess the affect of the implants on monocyte activation. Implants under conditions of inflammatory stress exhibited more negative E(corr) values, suggesting an increased potential for corrosion. Linear polarization measurements detected increased corrosion rates in the presence of elevated dextrose conditions over PBS conditions. EIS measurements suggested that implants underwent surface passivation reactions that may have limited corrosion over the short term of this test. This result was supported by cyclic polarization tests. IL-1beta secretion was not altered under conditions of corrosion or implant exposure. The results suggest that inflammatory stress and hyperglycemia may increase the corrosion of dental endosseous titanium-based implants, but that longer, more aggressive electrochemical conditions may be necessary to fully assess these effects.
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PMID:Corrosion of machined titanium dental implants under inflammatory conditions. 1856 Dec 92

A link between altered levels of various gangliosides and the development of insulin resistance was described in transgenic mice. Naturally occurring glycosphingolipids were shown to exert immunomodulatory effects in a natural killer T (NKT) cell-dependent manner. This study examined whether glycosphingolipid-induced modulation of the immune system may reduce pancreatic and liver steatosis and stimulate insulin secretion in the Cohen diabetes-sensitive (CDS) rat, a lean model of non-insulin-resistant, nutritionally induced diabetes. Four groups of CDS rats fed a diabetogenic diet were treated with daily intraperitoneal injections of glycosphingolipids beta-glucosylceramide, beta-lactosylceramide, a combination of both (IGL), or vehicle (PBS) for up to 45 days. Immune modulation was assessed by fluorescence-activated cell sorting analysis of intrahepatic and intrasplenic lymphocytes. Steatosis was assessed by MRI imaging and histological examination of liver and pancreas, Blood glucose and plasma insulin concentrations were assessed during an oral glucose tolerance test. Administration of glycosphingolipids, particularly IGL, increased intrahepatic trapping of CD8 T and NKT lymphocytes. Pancreatic and liver histology were markedly improved and steatosis was reduced in all treated groups compared with vehicle-treated rats. Insulin secretion was restored after glycosphingolipid treatment, resulting in improved glucose tolerance. The immunomodulatory effect of beta-glycosphingolipids improved the beta-cell function of the hyperglycemic CDS rat. Thus our results suggest a role for the immune system in the pathogenesis of diabetes in this model.
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PMID:Beta-glycosphingolipids improve glucose intolerance and hepatic steatosis of the Cohen diabetic rat. 1894 Sep 39

Cell-based therapies offer considerable promise for prevention or cure of diabetes. We explored the potential of autologous, self-renewing, mesenchymal stem cells (MSC) as a clinically-applicable approach to promote glucose homeostasis. In vitro-expanded syngeneic bone marrow-derived MSC were administered following or prior to diabetes induction into a rat model of streptozotocin-induced beta cell injury. MSC were CD45(-)/CD44(+)/CD54(+)/CD90(+)/CD106(+). MSC spontaneously secreted IL-6, HGF, TGF-beta1 and expressed high levels of SDF-1 and low levels of VEGF, IL-1beta and PGE(2), but no EGF, insulin or glucagon. MSC homed to the pancreas and this therapy allowed for enhanced insulin secretion and sustained normoglycemia. Interestingly, immunohistochemistry demonstrated that, the islets from MSC-treated rats expressed high levels of PDX-1 and that these cells were also positive for insulin staining. In addition, peripheral T cells from MSC-treated rats exhibited a shift toward IL-10/IL-13 production and higher frequencies of CD4(+)/CD8(+) Foxp3(+) T cells compared to the PBS-treated rats. These data suggest that the bioactive factors secreted by MSC establish a tissue microenvironment that supports beta cell activation/survival in the pancreas. In addition, because of anti-inflammatory and immunoregulatory effects of MSC on T cells, this work can lead to clinical trial of autologous MSC to prevent/cure type-1 diabetes.
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PMID:Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. 1906 54

A membrane receptor, Fas (CD95), and its ligand FasL have been considered as key players in diabetes pathogenesis. They are known to mediate interactions between beta cells and cytotoxic T cells, which results in apoptotic cell death. We hypothesized that the interruption of Fas-FasL interactions by suppressing Fas expression in beta cells would affect the development of diabetes. The effect of Fas-silencing siRNA (Fas siRNA) on diabetes development was evaluated in a cyclophosphamide (CY)-accelerated diabetes animal model after intravenous administration using a polymeric carrier, polyethylenimine (PEI). The systemic non-viral delivery of Fas siRNA showed significant delay in diabetes incidence up to 40 days, while the control mice treated with naked Fas siRNA, scrambled dsRNA, or PBS were afflicted with diabetes within 20 days. The retardation of diabetes incidence after the treatment of Fas siRNA may be due to the delayed progression of the pancreatic insulitis. In this study, the potential use of a non-viral carrier based siRNA gene therapy for the prevention of type-1 diabetes is demonstrated.
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PMID:Non-viral systemic delivery of Fas siRNA suppresses cyclophosphamide-induced diabetes in NOD mice. 2000 92

We have reported that GM-CSF treatment of NOD mice suppressed diabetes by increasing the number of tolerogenic dendritic cells (tDCs) and Tregs in the periphery. Here, we have investigated whether GM-CSF acted on NOD bone marrow DCs precursors to skew their differentiation to tDCs. DCs were generated from the bone marrow of GM-CSF-treated (GM.BMDCs) and PBS-treated (PBS.BMDCs) NOD mice and were assessed for their ability to acquire tolerogenic properties. Upon LPS stimulation, GM.BMDCs became fully mature, expressed high levels of PD-L1 and produced more IL-10 and less IL-12p70 and IFN-gamma than PBS.BMDCs. In addition, LPS-stimulated GM.BMDCs possessed a reduced capacity to activate diabetogenic CD8(+) T cells in a PD-1/PD-L1-dependent manner. A single injection of LPS-stimulated GM.BMDCs in NOD mice resulted in long-term protection from diabetes, in contrast to LPS-stimulated PBS.BMDCs. Our results showed that GM-CSF-treatment acted on bone marrow precursors to skew their differentiation into tDCs that protected NOD mice against diabetes.
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PMID:GM-CSF induces bone marrow precursors of NOD mice to skew into tolerogenic dendritic cells that protect against diabetes. 2063 54

Transplantation of human cord blood-derived endothelial progenitor cells (EPCs) is reported to contribute to neovascularization in various ischemic diseases. However, the possible beneficial role and underlying mechanisms in diabetes-impaired wound healing have been less well characterized. In this study, EPC transplantation stimulated keratinocyte and fibroblast proliferation substantially as early as 3 days after injury, leading to significantly accelerated wound closure in streptozotocin-induced diabetic nude mice, compared to PBS control. RT-PCR analysis showed that EPCs secreted various wound healing-related growth factors. Among them, keratinocyte growth factor and platelet-derived growth factor were highly expressed in the EPCs and were present at substantial levels in the EPC-injected dermal tissue. Using EPC-conditioned medium (CM), we found that paracrine factors from EPCs directly exerted mitogenic and chemotactic effects on keratinocytes and fibroblasts. Moreover, injection of EPC-CM alone into the same diabetic wound mice promoted wound healing and increased neovascularization to a similar extent as achieved with EPC transplantation. These results indicate that the beneficial effect of EPC transplantation on diabetic wounds was mainly achieved by their direct paracrine action on keratinocytes, fibroblasts, and endothelial cells, rather than through their physical engraftment into host tissues (vasculogenesis). In addition, EPC-CM was shown to be therapeutically equivalent to EPCs, at least for the treatment of diabetic dermal wounds, suggesting that conditioned medium may serve as a novel therapeutic option that is free from allograft-associated immune rejection concern.
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PMID:Human cord blood-derived endothelial progenitor cells and their conditioned media exhibit therapeutic equivalence for diabetic wound healing. 2065 57

This study was designed to investigate the effect of vascular endothelial growth factor 164 adenovirus (Ad-VEGF(164))-transfected mesenchymal stem cells (MSC) on improving erectile function in diabetic rats. Forty-five male Sprague-Dawley rats were injected with streptozotocin to develop type 1 diabetes, whereas 10 served as normal controls. Diabetic rats were randomly divided into 3 groups: rats that underwent intracavernous injection with phosphate-buffered saline (DM+PBS), unmodified MSCs (DM+MSC), and Ad-VEGF(164)-transfected MSCs (DM+VMSC). Normal controls received intracavernous injection of PBS. Four weeks after injection, erectile function was measured by cavernous nerve electrostimulation. Penile tissue was harvested for histology and enzyme-linked immunoassay. Prior to injection, high expression of VEGF was confirmed in Ad-VEGF(164)-transfected MSCs by enzyme-linked immunoassay. Four weeks after injection, the erectile function, as well as the content of smooth muscle and endothelium in corpus cavernosum increased significantly in the MSC-injected groups compared with the DM+PBS group. There was a significant improvement of erectile function, the content of smooth muscle and endothelium, and the VEGF concentration in the corpus cavernosum in the DM+VMSC group compared with the DM+MSC group. Our study validates the effect of intracavernous injection of MSCs for diabetes-associated erectile dysfunction in an animal model. The combined strategy of MSC injection with VEGF gene therapy-enhanced therapy of MSCs for the treatment of diabetes-associated erectile dysfunction.
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PMID:Combined strategy of mesenchymal stem cell injection with vascular endothelial growth factor gene therapy for the treatment of diabetes-associated erectile dysfunction. 2131 Oct 50

To examine the histological changes of diabetic rats' skin and the effects on the percutaneous absorption of hydrocortisone (HC, a glucocorticoid), male Wistar rats were randomly divided into five groups: control group, diabetes one-week group (W1), two-week group (W2), three-week group (W3), and four-week group (W4), while each group contained 6 rats. Diabetes mellitus (DM) rat model was prepared with the method of streptozocin (STZ, 40 mg x kg(-1)) intraperitoneal injection. Abdominal skin was cut to carry out an in-vitro penetration experiment on an improved Franz diffusion cells, and phosphate buffer (PBS, pH 7.4) was used as receptor solution. The solution was analyzed with HPLC, and then the penetrating rate can be calculated. Meanwhile, rats' abdominal skins of different DM periods were HE stained and made into tissue slices to find if any histological changes occurred. The penetrating rate of control, W1, W2, W3, and W4 groups were 2.39 +/- 1.25, 3.22 +/- 1.72, 3.02 +/- 1.89, 3.63 +/- 2.02 and 5.00 +/- 3.36 microg x h(-1) x cm(-2), respectively. There was significant difference between the control and the W4 group (P < 0.05), but no significant differences were found between any other two groups (P > 0.05). The tissue slices showed that compared to the normal rats' skin, little change was observed in one-week DM rats' skin, but the skin of one-month DM rats' skin was observed thinner, and it became much thinner than that of rats with two-month diabetes, especially the epidermis. After making a rat into diabetic, the rats' skin goes through a pathological change, and this change is closely interrelated with the increase of the permeation of HC. Therefore, it is necessary to adjust the dose while some drug was applied on the skin in case of diabetes mellitus.
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PMID:[The histological changes of diabetic rats' skin and the effects on the percutaneous absorption of glucocorticoid]. 2135 60

Instant blood-mediated inflammatory reaction (IBMIR) causes rapid islet loss in islet transplantation. Endothelial colony-forming cells (ECFCs) display unique abilities to promote angiogenesis and repair vascular injury compared to those of endothelial cells (ECs), which inhibits the allogeneic and xenogeneic IBMIR. We investigated the coating of pig islets with ex vivo-expanded ECFCs as a strategy to overcome xenogeneic IBMIR. Porcine islets were cocultured with human ECFCs in a specially modified culture medium for 2 days to obtain 70-90% coverage. The coating of pig islets with human ECFCs did not affect the glucose-stimulated insulin secretion capacity or diabetes reversal rate after the transplantation of a marginal islet mass under the kidney capsules of diabetic nude mice compared to that of untreated islets. Uncoated islets, PBS control without islets, and the ECFC-coated islets were examined with an in vitro tubing loop assay using human blood. After 60 min of incubation in human blood, the ECFC-coated islets showed platelet consumption inhibition and low C3a and TAT assay results compared to those of the uncoated islets. Furthermore, there was very little macroscopic or microscopic clotting in the human ECFC-coated pig islets. The protective effect was more prominent compared to that of human EC coating of pig islets in our previous study. We investigated the changes in human-specific MCP-1, IL-8, and tissue factor (TF) levels after the coating of pig islets with human ECFCs or human ECs. The IL-8 levels after coating pig islets with ECFCs were significantly lower than those after coating pig islets with ECs, but there were no significant differences in the MCP-1 or TF levels between the ECFCs and ECs. In conclusion, the coating of pig islets with ECFCs completely prevented all components of xenogeneic IBMIR. ECFCs may be a better source of protection against xenogeneic IBMIR than are mature ECs.
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PMID:Endothelial colony-forming cell coating of pig islets prevents xenogeneic instant blood-mediated inflammatory reaction. 2139 65


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