Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Diabetes mellitus type I was induced in 3-month old male C57 BL/KS-mdb mice (N = 24) by ip injection of streptozotocin (STZ, 45 mg/kg body weight) for 5 days. 2. To determine the possible protective effects of nitric oxide inhibition against hyperglycemia, the STZ-diabetic rats received two doses of NG-nitro-L-arginine- methyl ester (L-NAME) (10 mg/kg body weight and 10 mg/mouse) dissolved in PBS for 45 consecutive days. Another group of STZ-treated rats was similarly treated with L-arginine (5 mg/mouse). 3. Blood glucose levels were 118 +/- 37 mg/dl after 8 days of L-NAME administration (10 mg/kg body weight, N = 12) and 186 +/- 22 mg/dl (N = 12) after 5 days of L-NAME administration at the 5 mg/mouse dose. Treatment with L-arginine (5 mg/mouse, N = 12) caused a significant increase in blood glucose level to 151 +/- 17.5 mg/dl, showing the relevance of nitric oxide formation in this type of diabetes. 4. In STZ-diabetic mice treated with L-NAME (N = 12), diuresis was reduced by approximately 58% compared to STZ animals, whereas in L-arginine-treated animals (N = 12) diuresis returned to STZ levels. Urinary protein excretion, which was significantly affected by STZ (123% compared to control) was significantly reduced by 66% after treatment with L-NAME for 45 days, whereas treatment with L-arginine caused a return to STZ values. 5. Urinary kallikrein excretion, which was reduced by 80% in STZ mice compared to control, returned to control levels after L-NAME treatment. 6. The present results suggest a relationship between nitric oxide levels and the reduction of diabetic state and improved renal function by L-NAME.
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PMID:Streptozotocin-induced hyperglycemia is decreased by nitric oxide inhibition. 774 93

Insulin-dependent diabetics have a greatly increased risk of developing premature coronary artery disease which is not entirely explained by known risk factors. A possible explanation may be enhanced oxidative modification of low density lipoprotein (LDL). The aim of this study was to determine firstly, whether or not LDL from moderately well controlled type 1 diabetics is more readily oxidisable than LDL from healthy non-diabetics and, secondly, to assess whether potential predictors of LDL oxidisability differ between type 1 diabetics and controls. Twenty type 1 diabetic men were carefully matched with healthy non-diabetic men on the basis of age and body mass index and each pair attended the department on the same morning for blood sampling. LDL oxidisability was assessed using both copper in PBS, 15 and 30 mM glucose, and with AAPH. There was no difference between type 1 diabetics and controls in the susceptibility of the LDL to either copper-dependent or non-transition metal-dependent oxidation. Furthermore, there was no difference between the groups for LDL vitamin E content, LDL fatty acid composition in cholesteryl esters, triglycerides or phospholipids, or LDL copper reductive capacity, but LDL glycation was elevated in the IDDM subjects. Given the absence of increased LDL oxidisability in these subjects, the recommendation of vitamin E supplementation in type 1 diabetics should be considered a secondary priority to achieving adequate glucose control.
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PMID:Absence of increased susceptibility of LDL to oxidation in type 1 diabetics. 886 59

Heat shock protein 65 (hsp65) and a derived peptide, p277, are autoantigens reported in IDDM. I.p. injection of hsp65 reduced diabetes incidence in NOD mice and administration of p277 cured already diabetic mice. Also, intrathymic (i.t.) administration of whole islets or GAD65 prevented diabetes in NOD mice. The aim of this study was to evaluate whether i.t. injection of mycobacterial hsp65 or p277 can prevent diabetes in NOD mice. Three-week-old NOD female mice were injected intrathymically with 50 microg of hsp65 (n=30), 5 microg of p277 (n=30), and PBS (n=29). Diabetes incidence was observed for the following 300 days. Pancreas was then used for histological and immunohistological evaluation. No significant differences in diabetes incidence were observed among the three groups of mice. Interestingly, hsp65-treated mice developed diabetes slightly faster at 177+/-6 days compared to 202+/-8 days (p=0.015) for the p277-treated group and 197+/-7 days (p=0.033) for controls. The insulitis score and average islet size did not differ significantly among the three groups of diabetic mice. Scattered TCR-gamma/delta positive cells were found in the pancreas of all groups of mice. In contrast, a huge infiltrate of TCR-gamma/delta positive cells was detected in four out of eight (50%) p277-diabetic NOD mice. Thus, our data show an earlier onset of diabetes in hsp65-treated mice and no improvement in the incidence with either hsp65 or p277, suggesting that hsp65 acts in a different way from what was reported with GAD65. Caution is advised in future vaccination studies as hsp65 poses a potential danger.
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PMID:Effect of intrathymic administration of mycobacterial heat shock protein 65 and peptide p277 on the development of diabetes in NOD mice: caution required in vaccination studies. 983 5

We studied the effect of high-dose mouse IgG on TMEV-induced demyelinating disease (TMEV-IDD). We injected TMEV intracerebrally into susceptible SJL/J mice and induced TMEV-IDD. Mouse IgG were injected intraperitonealy, and clinical course and various immunological indicators were studied. The results show that TMEV-IDD was significantly suppressed both clinically and histologically (P<0.01) when IgG were administered in the effector phase. The delayed type hypersensitivity and T cell proliferative response specific for TMEV were decreased by this treatment. In an ELISPOT assay, the number of TNF-alpha producing lymphocytes in the spinal cords was low in high-dose IgG treated mice compared with PBS treated control mice. These data suggest that administration of IgG suppresses TMEV-IDD and may be promising treatment to prevent exacerbation of human multiple sclerosis.
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PMID:High-dose mouse immunoglobulin G administration suppresses Theiler's murine encephalomyelitis virus-induced demyelinating disease. 1090 Mar 33

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

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.
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PMID:Transfusion of apoptotic beta-cells induces immune tolerance to beta-cell antigens and prevents type 1 diabetes in NOD mice. 1749 35

Although B cells play a pathogenic role in the initiation of type 1 diabetes (T1D) in NOD mice, it is not known whether activated B cells can maintain tolerance and transfer protection from T1D. In this study, we demonstrate that i.v. transfusion of BCR-stimulated NOD spleen B cells into NOD mice starting at 5-6 wk of age both delays onset and reduces the incidence of T1D, whereas treatment initiated at 9 wk of age only delays onset of T1D. This BCR-activated B cell-induced protection from T1D requires IL-10 production by B cells, as transfusion of activated B cells from NOD.IL-10(-/-) mice does not confer protection from T1D. Consistent with this result, severe insulitis was observed in the islets of NOD recipients of transfused NOD.IL-10(-/-) BCR-stimulated B cells but not in the islets of NOD recipients of transfused BCR-stimulated NOD B cells. The therapeutic effect of transfused activated NOD B cells correlates closely with the observed decreased islet inflammation, reduced IFN-gamma production and increased production of IL-4 and IL-10 by splenocytes and CD4(+) T cells from NOD recipients of BCR-stimulated NOD B cells relative to splenocytes and CD4(+) T cells from PBS-treated control NOD mice. Our data demonstrate that transfused BCR-stimulated B cells can maintain long-term tolerance and protect NOD mice from T1D by an IL-10-dependent mechanism, and raise the possibility that i.v. transfusion of autologous IL-10-producing BCR-activated B cells may be used therapeutically to protect human subjects at risk for T1D.
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PMID:Intravenous transfusion of BCR-activated B cells protects NOD mice from type 1 diabetes in an IL-10-dependent manner. 1802 64

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

Type 1 diabetes is an insulin-dependent metabolic disorder always associated with ketoacidosis and a high morbidity rate in teenagers. The in situ single molecule detection of insulin receptors on healthy and diseased erythrocytes is helpful to understand the pathomechanism of type 1 diabetes ketoacidosis (T1-DKA), which would also benefit the diagnosis and treatment of T1-DKA. Here, we demonstrated, for the first time, the single molecule interaction between insulin and insulin receptor on erythrocytes from a healthy volunteer and a T1-DKA patient using high sensitivity atomic force microscopy (AFM) in PBS solution. The single molecule force results demonstrated the decreased binding force and binding probability between insulin and insulin receptor on T1-DKA erythrocytes, implying the deficit of insulin receptor functions in T1-DKA. The binding kinetic parameters calculated from dynamic force spectroscopy indicated that the insulin-insulin receptor complexes on T1-DKA erythrocytes were less stable than those from healthy volunteer. Using high resolution AFM imaging, a decreased roughness was found both in intact T1-DKA erythrocytes and in the purified membrane of T1-DKA erythrocytes, and an increased stiffness was also found in T1-DKA erythrocytes. Moreover, AFM, which was used to investigate the single molecule interactions between insulin-insulin receptor, cell surface ultrastructure and stiffness in healthy and diseased erythrocytes, was expected to develop into a potential nanotool for pathomechanism studies of clinical samples at the nanoscale.
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PMID:In situ single molecule detection of insulin receptors on erythrocytes from a type 1 diabetes ketoacidosis patient by atomic force microscopy. 2640 19

Studies have shown oral insulin prevents type 1 diabetes (T1D) in mouse models, however human trials were inconclusive. We tested the ability of different insulins to prevent T1D in non-obese diabetic mice. Mice received oral insulin or PBS twice weekly and disease was monitored. Contrary to previous studies, no insulin tested showed significant ability to prevent T1D, nor did testing of linked suppression in a delayed type hypersensitivity model have reproducible effect. To investigate delivery of antigen within the GI tract, blue dye was fed to mice. Dye traveled 5-8 cm from stomach to small intestine within 10s, suggesting orally administered antigen may not get digested in the stomach in mice. Insulin incubated with jejunum extracts was instantly digested. Thus, in humans large doses of insulin may be required to achieve tolerance as antigen may be more vulnerable to digestion in the stomach even before reaching the small intestine.
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PMID:Oral insulin (human, murine, or porcine) does not prevent diabetes in the non-obese diabetic mouse. 2682 3


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