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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this work was to investigate the effects of Aloe vera leaf pulp and gel extracts on the liver tissue of neonatal streptozotocin (n0STZ)-induced type-II diabetic rats. The diabetic rats were separated into four groups and each group was given the following samples by gavage, daily for 15 d: phosphate buffered saline (PBS; diabetic control), Aloe leaf pulp extract, Aloe leaf gel extract, glibenclamide. Liver tissues were examined histologically. The markers of oxidative stress: glutathione (GSH), non-enzymatic glycosylation (NEG) and lipid peroxidation (LPO), were determined in liver tissue. Biochemical parameters for liver function: serum alkaline phosphatase (ALP), and alanine transaminase (ALP) activities, were evaluated. All parameters were also determined in healthy (non diabetic) rats for comparison. In the diabetic control group, the degenerative changes in liver tissue were remarkable, while in the diabetic groups given Aloe pulp and gel extracts and glibenclamide, the damage to the liver tissue was decreased. The increase of GSH and the decrease of NEG and LPO in liver tissues with the treatment of Aloe gel extract, is consistent with the beneficial effect of Aloe. Serum ALP and ALT activities were also decreased in the groups given Aloe gel extract. It was concluded that Aloe gel extract has a protective effect comparable to glibenclamide against hepatotoxicity produced by diabetes if used in the treatment of type-II diabetes.
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PMID:Effect of Aloe vera leaf gel and pulp extracts on the liver in type-II diabetic rat models. 1513 47

Macrophages play a critical role in the pathogenesis of Kilham rat virus (KRV)-induced autoimmune diabetes in diabetes-resistant BioBreeding (DR-BB) rats. This investigation was initiated to determine the role of macrophage-derived soluble mediators, particularly NO, in the pathogenesis of KRV-induced diabetes in DR-BB rats. We found that the expression of inducible NO synthase (iNOS), an enzyme responsible for NO production, was significantly increased during the early phase of KRV infection. Inhibition of iNOS by aminoguanidine (AG) treatment resulted in the prevention of diabetes in KRV-infected animals. The expression of IL-1beta, TNF-alpha, and IL-12 was significantly decreased in the spleen of AG-treated, KRV-infected DR-BB rats compared with PBS-treated, KRV-infected control rats. Subsequent experiments revealed that AG treatment exerted its preventive effect in KRV-infected rats by maintaining the finely tuned immune balance normally disrupted by KRV, evidenced by a significant decrease in the expression of IFN-gamma, but not IL-4, and a decrease in Th1-type chemokine receptors CCR5, CXCR3, and CXCR4. We also found that iNOS inhibition by AG decreased the KRV-induced expression of MHC class II molecules and IL-2R alpha-chain, resulting in the suppression of T cell activation, evidenced by the decreased cytolytic activity of CD8(+) T cells. We conclude that NO plays a critical immunoregulatory role by up-regulating macrophage-derived proinflammatory cytokines, up-regulating the Th1 immune response, and activating T cells, leading to type 1 diabetes after KRV infection, whereas suppression of NO production by AG treatment prevents KRV-induced autoimmune diabetes in DR-BB rats.
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PMID:Immunoregulatory role of nitric oxide in Kilham rat virus-induced autoimmune diabetes in DR-BB rats. 1524 Jul 27

NKT cell activation by alpha-galactosylceramide (alpha-GalCer) inhibits autoimmune diabetes in NOD mice, in part by inducing recruitment to pancreatic lymph nodes (PLNs) of mature dendritic cells (DCs) with disease-protective effects. However, how activated NKT cells promote DC maturation, and what downstream effect this has on diabetogenic T cells was unknown. Activated NKT cells were found to produce a soluble factor(s) inducing DC maturation. Initially, there was a preferential accumulation of mature DCs in the PLNs of alpha-GalCer-treated NOD mice, followed by a substantial increase in T cells. Adoptive transfer of a diabetogenic CD8 T cell population (AI4) induced a high rate of disease (75%) in PBS-treated NOD recipients, but not in those pretreated with alpha-GalCer (8%). Significantly, more AI4 T cells accumulated in PLNs of alpha-GalCer than PBS-treated recipients, while no differences were found in mesenteric lymph nodes from each group. Compared with those in mesenteric lymph nodes, AI4 T cells entering PLNs underwent greater levels of apoptosis, and the survivors became functionally anergic. NKT cell activation enhanced this process. Hence, activated NKT cells elicit diabetes protection in NOD mice by producing a soluble factor(s) that induces DC maturation and accumulation in PLNs, where they subsequently recruit and tolerize pathogenic T cells.
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PMID:Activated NKT cells inhibit autoimmune diabetes through tolerogenic recruitment of dendritic cells to pancreatic lymph nodes. 1566 73

Recent studies have demonstrated that the transplantation of bone marrow cells following diabetes induced by streptozotocin can support the recovery of pancreatic b-cell mass and a partial reversal of hyperglycemia. To address this issue, we examined whether the c-Met/hepatocyte growth factor (HGF) signaling pathway was involved in the recovery of b-cell injury after bone marrow transplantation (BMT). In this model, donor-derived bone marrow cells were positive for HGF immunoreactivity in the recipient spleen, liver, lung, and pancreas as well as in the host hepatocytes. Indeed, plasma HGF levels were maintained at a high value.The frequency of c-Met expression and its proliferative activity and differentiative response in the pancreatic ductal cells in the BMT group were greater than those in the PBS-treated group, resulting in an elevated number of endogenous insulin-producing cells. The induction of the c-Met/HGF signaling pathway following BMT promotes pancreatic regeneration in diabetic rats.
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PMID:Hepatocyte growth factor is constitutively produced by donor-derived bone marrow cells and promotes regeneration of pancreatic beta-cells. 1595 Jan 93

In recent years, several investigators have shown that transfer of dendritic cells (DC) prevents diabetes development in non-obese diabetic (NOD) mice. Accumulating evidences showing that DC cultured in medium containing fetal calf serum (FCS) can induce a dominant unspecific immune response in tumor models after i.v. injection prompted us to investigate if the protecting effect of DC on diabetes development in NOD mice might be supported by the induction of an anti-FCS immune response in recipient mice. Five-week-old NOD mice were injected i.v. with FCS-cultured bone marrow-derived DC or PBS as control. Levels of anti-FCS and anti-bovine serum albumin (BSA) antibodies were measured in the serum of recipient mice. Anti-FCS cellular immune responses were also analysed after a single DC injection using in vitro proliferation of splenocytes either in RPMI supplemented with FCS, AIMV-BSA or RPMI containing autologous mouse serum or BSA as a read out. DC injection prevented diabetes development in NOD mice and high titers of anti-FCS and anti-BSA antibodies were detected in serum of all DC-injected mice. Besides, splenocytes isolated from DC-injected mice proliferated vigorously in the presence of bovine proteins in contrast to splenocytes isolated from control mice but removing bovine proteins abrogated the high level of proliferation of those splenocytes suggesting that lymphocytes have been primed against bovine proteins in vivo after DC injection. All together, our data show that DC transfer induced cellular and humoral anti-FCS immune responses in recipient NOD mice suggesting that the protective effect of DC relies on their unspecific immunostimulatory effects.
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PMID:Fetal calf serum-primed dendritic cells induce a strong anti-fetal calf serum immune response and diabetes protection in the non-obese diabetic mouse. 1719 60

Diabetic nephropathy, a major complication of diabetes mellitus that leads to mortality, has been shown to involve a dysregulation of the coagulation system. Annexin-2, a co-receptor for plasminogen and tissue plasminogen activator on endothelial cells, is one of the molecules required to maintain the antithrombogenic properties of endothelial cells. Previously, we showed that recombinant annexin-2 protein (rAN II) modulated impaired fibrinolytic activity in the carotid arteries of rats. In the present study, to investigate its protective effects against diabetic nephropathy, rAN II was administered to KK-Ay mice, a murine model of type 2 diabetes, for eight weeks, and albuminuria, kidney size, and histological glomerular lesions were investigated. The mean weight of kidneys from KK-Ay mice treated with rAN II was significantly less than that of those treated with PBS (control) (p < 0.02). Furthermore, the level of albuminuria observed in rAN II-treated KK-Ay mice was significantly less than that of the control group (rAN II, 0.90+/-0.12 microg/day; PBS, 1.55+/-0.31 microg/day; p < 0.01); also, the area of diffuse glomerular lesions was significantly smaller (rAN II, 41.51+/-4.54%; PBS, 81.81+/-8.10%; p < 0.01). Bleeding time, prothrombin time (PT), and active partial thromboplastin time (APTT) did not significantly differ between the two groups. Our results suggest that rAN II may inhibit the progression of diabetic nephropathy in KK-Ay mice without influencing the coagulation system, indicating that annexin-2 may be considered as a possible new therapeutic tool for patients with diabetic nephropathy.
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PMID:Recombinant annexin-2 inhibits the progress of diabetic nephropathy in a diabetic mouse model via recovery of hypercoagulability. 1720 Jul 79

An increase in oxidizing response above a certain threshold produces, in the absence of a concomitant rise in antioxidant/reducing response, oxidative stress that is associated with complications in diabetes. A simple technique involving reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye has been developed in order to determine quantitatively the antioxidant status of plasma. MTT (50microL; 5.0mg/mL in PBS) was incubated with plasma (100microL) in PBS for 30, 60 or 120min at 37 degrees C, the reaction terminated by addition of 1.0mL of 0.04M hydrochloric acid in isopropanol and the absorbance measured at 570nm. The modulation by plasma of the generation of reactive oxygen species (ROS) in 12,13-phorbol dibutyrate (PDB)-stimulated granulocytes was evaluated using a chemiluminescence luminol-dependent assay. Plasma from healthy subjects (n=15) showed significantly higher antioxidant status (p<0.05) over all time periods studied compared with plasma from diabetic patients (n=27). MTT was directly reduced by plasma although platelets were not involved. Moreover, the reduction of MTT by bovine serum albumin at levels equivalent to the concentration of human serum albumin in plasma was much lower. The antioxidant status of plasma, as evaluated by MTT dye reduction, may reflect an antioxidant response since ROS generation in PDB-stimulated granulocytes was rapidly down-regulated by the presence of plasma (3.3-fold in diabetic patients and 5.8-fold in healthy subjects) confirming the lower antioxidant activity of plasma from diabetic patients. The results demonstrate that extracellular reduction of MTT by plasma may occur via enzymatic and non-enzymatic processes.
Diabetes Res Clin Pract 2007 Aug
PMID:Determination of the antioxidant status of plasma from type 2 diabetic patients. 1727 Mar 9

In vivo induction of beta-cell apoptosis has been demonstrated to be effective in preventing type 1 diabetes in NOD mice. Based on the notion that steady-state cell apoptosis is associated with self-tolerance and the need for developing a more practical approach using apoptotic beta-cells to prevent type 1 diabetes, the current study was designed to investigate apoptotic beta-cells induced ex vivo in preventing type 1 diabetes. The NIT-1 cell line serves as a source of beta-cells. Apoptotic NIT-1 cells were prepared by ultraviolet B (UVB) irradiation. Three weekly transfusions of UVB-irradiated NIT-1 cells (1 x 10(5)/mouse) or PBS were used to determine whether transfusions of UVB-irradiated NIT-1 cells induce immune tolerance to beta-cell antigens in vivo and prevent type 1 diabetes. The suppression of anti-beta-cell antibodies, polarization of T-helper (Th) cells, and induction of regulatory T-cells by UVB-irradiated NIT-1 cell treatment were investigated. The transfusions of apoptotic NIT-1 cells suppress anti-beta-cell antibody development and induce Th2 responses and interleukin-10-producing regulatory type 1 cells. Importantly, this treatment significantly delays and prevents the onset of diabetes when 10-week-old NOD mice are treated. Adoptive transfer of splenocytes from UVB-irradiated NIT-1 cell-treated mice prevents diabetes caused by simultaneously injected diabetogenic splenocytes in NOD-Rag(-/-) mice. Moreover, the proliferation of adoptively transferred carboxyfluorescein diacetate succinimidyl ester-labeled beta-cell antigen-specific T-cell receptor-transgenic T-cells in UVB-irradiated NIT-1-cell treated mice is markedly suppressed. The transfusion of apoptotic beta-cells effectively protects against type 1 diabetes in NOD mice by inducing immune tolerance to beta-cell antigens. This approach has great potential for immune intervention for human type 1 diabetes.
Diabetes 2007 Aug
PMID:Transfusion of apoptotic beta-cells induces immune tolerance to beta-cell antigens and prevents type 1 diabetes in NOD mice. 1749 35

The inhibitory effect of diallyl sulphide (DAS) and diallyl disulphide (DADS) against meticillin-resistant Staphylococcus aureus (MRSA) infection in diabetic mice was studied. The influence of these agents on the plasma levels of fibronectin, C-reactive protein (CRP), fibrinogen, interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-alpha), and on the activity of plasminogen activator inhibitor-1 (PAI-1), antithrombin III (AT-III) and protein C, in MRSA-infected diabetic mice was examined. To induce diabetes, mice were treated intraperitoneally with streptozotocin for 5 consecutive days. Ten clinical MRSA isolates obtained from infected patients were used in this study. Diabetic mice were infected by injecting 200 microl MRSA/PBS suspension containing 10(7) c.f.u. via the tail vein. At day 4 post-infection, 200 microl DAS or DADS was administrated twice orally with an interval of 12 h. Eight hours after each administration, the blood and organs of mice were collected. Results showed that DAS and DADS significantly decreased MRSA viability in the kidney (P<0.05), with administration of each agent twice showing a greater inhibitory effect than when given once (P<0.05). MRSA infection in diabetic mice significantly elevated the plasma levels of IL-6 and TNF-alpha (P<0.05). DAS or DADS given once did not affect the plasma levels of IL-6 and TNF-alpha (P>0.05); however, DAS or DADS given twice significantly decreased the plasma levels of both IL-6 and TNF-alpha (P<0.05). DAS and DADS treatments also significantly reduced the plasma levels of CRP, fibronectin and fibrinogen (P<0.05). DAS or DADS treatment did not affect PAI-1 activity (P>0.05), but DAS or DADS given twice significantly increased AT-III activity (P<0.05). DADS given twice elevated protein C activity (P<0.05). MRSA infection significantly increased malondialdehyde levels in the kidney and spleen (P<0.05), and these levels were significantly decreased by treatment with DAS or DADS (P<0.05). These data suggest that DAS and DADS could provide multiple protective functions against MRSA infection in diabetic mice.
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PMID:Two diallyl sulphides derived from garlic inhibit meticillin-resistant Staphylococcus aureus infection in diabetic mice. 1751 Feb 66

Autoimmune diabetes results from a breakdown of self-tolerance that leads to T cell-mediated beta-cell destruction. Abnormal maturation and other defects of dendritic cells (DCs) have been associated with the development of diabetes. Evidence is accumulating that self-tolerance can be restored and maintained by semimature DCs induced by GM-CSF. We have investigated whether GM-CSF is a valuable strategy to induce semimature DCs, thereby restoring and sustaining tolerance in NOD mice. We found that treatment of prediabetic NOD mice with GM-CSF provided protection against diabetes. The protection was associated with a marked increase in the number of tolerogenic immature splenic DCs and in the number of Foxp3+CD4+CD25+ regulatory T cells (Tregs). Activated DCs from GM-CSF-protected mice expressed lower levels of MHC class II and CD80/CD86 molecules, produced more IL-10 and were less effective in stimulating diabetogenic CD8+ T cells than DCs of PBS-treated NOD mice. Adoptive transfer experiments showed that splenocytes of GM-CSF-protected mice did not transfer diabetes into NOD.SCID recipients. Depletion of CD11c+ DCs before transfer released diabetogenic T cells from the suppressive effect of CD4+CD25+ Tregs, thereby promoting the development of diabetes. These results indicated that semimature DCs were required for the sustained suppressive function of CD4+CD25+ Tregs that were responsible for maintaining tolerance of diabetogenic T cells in NOD mice.
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PMID:Granulocyte-macrophage colony-stimulating factor prevents diabetes development in NOD mice by inducing tolerogenic dendritic cells that sustain the suppressive function of CD4+CD25+ regulatory T cells. 1778 99


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