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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DBA/2 mice treated with anti-Mac1 monoclonal antibody (MAb) failed to develop encephalomyocarditis virus (EMCV)-induced diabetes and myocarditis. Virus concentrations and the number of viral RNA-positive cells in the pancreas and heart were significantly reduced in mice treated with anti-Mac1 MAb. Mac1-positive macrophages seem to be involved in EMCV-induced disease and to affect the replication of EMCV in target organs.
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PMID:Depletion of Mac1-positive macrophages protects DBA/2 mice from encephalomyocarditis virus-induced myocarditis and diabetes. 862 62

The role of macrophages in the development of diabetes following infection with encephalomyocarditis (EMC) virus was examined in 3 strains of mice (DBA/2 and BALB/c: susceptible, C57BL/6: resistant). After infection with 100 plaque forming units (PFU)/head of EMC-D (highly diabetogenic variant), the incidence of diabetes at 3 days post infection (DPI) (DBA/2: 7/8, BALB/c: 3/8, C57BL/6: 0/8) was well correlated with the severity of macrophage infiltration with beta cell damage in the pancreatic islets (DBA/2: sever, BALB/c: moderate, C57BL/6: slight). Silica-pretreatment depleted macrophage infiltration in the pancreatic islets and decreased the incidence of diabetes at 7 DPI from 100% to 40% in DBA/2 and from 80% to 0% in BALB/c mice, respectively. These results suggest that macrophages play a critical role in the process of pancreatic beta cell damage in EMC virus infection in mice.
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PMID:Involvement of macrophages in the development of encephalomyocarditis (EMC) virus-induced diabetes in mice. 868 84

Pancreatic islets from DBA/2 mice infected with the D variant of encephalomyocarditis (EMC-D) virus revealed lymphocytic infiltration with moderate to severe destruction of pancreatic beta cells. Our previous studies showed that the major population of infiltrating cells at the early stages of infection is macrophages. The inactivation of macrophages prior to viral infection resulted in the prevention of diabetes, whereas activation of macrophages prior to viral infection resulted in the enhancement of beta-cell destruction. This investigation was initiated to determine whether macrophage-produced soluble mediators play a role in the destruction of pancreatic beta cells in mice infected with a low dose of EMC-D virus. When we examined the expression of the soluble mediators interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) in the pancreatic islets, we found that these mediators were clearly expressed at an early stage of insulitis and that this expression was evident until the development of diabetes. We confirmed the expression of these mediators by in situ hybridization with digoxigenin-labelled RNA probes or immunohistochemistry in the pancreatic islets. Mice treated with antibody against IL-1beta or TNF-alpha or with the iNOS inhibitor aminoguanidine exhibited a significant decrease in the incidence of diabetes. Mice treated with a combination of anti-IL-1beta antibody, anti-TNF-alpha antibody, and aminoguanidine exhibited a greater decrease in the incidence of disease than did mice treated with one of the antibodies or aminoguanidine. On the basis of these observations, we conclude that macrophage-produced soluble mediators play an important role in the destruction of pancreatic beta cells, resulting in the development of diabetes in mice infected with a low dose of EMC-D virus.
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PMID:Possible role of macrophage-derived soluble mediators in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. 909 80

In an IDDM model mouse which was inoculated with a diabetogenic variant, DK-27, of encephalomyocarditis (EMC) virus, the relation between a stable glycated hemoglobin A1C (St-HbA1C) level and plasma glucose level (PGL) in the progress of diabetes was studied. The St-HbA1C level and PGL were examined every 2 weeks for 10 weeks in normal male DBA/2 and IDDM-onset mice. PGLs of normal control mice did not change, but their St-HbA1C levels were slightly increased by 0.52 to 1.03%. On the other hand, in IDDM mice, their PGLs were greatly increased (> 400 mg/dl) and hyperglycemia was maintained throughout this observation period, with their St-HbA1C noticeably increased to 3.8% according to the progress of diabetes for 10 weeks. A highly significant correlation between St-HbA1C levels and averaged PGLs for the past weeks was found in IDDM mice. To examine the reflection of St-HbA1C levels to delicately varied PGLs, we also estimated both values in IDDM mice which were treated with insulin at a minimal effective dose once a day for 4 weeks. The St-HbA1C levels in insulin-injected IDDM mice were significantly lower than those in control IDDM mice. These findings suggest that the estimation of the St-HbA1C level is useful in following up blood glucose control in a long-term therapeutical study with small laboratory animals.
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PMID:Relation between stable glycated hemoglobin A1C and plasma glucose levels in diabetes-model mice. 914 93

The effects of 4 weeks' administration of pramlintide, an analogue of the human hormone amylin, on blood glucose control in 215 patients with insulin-dependent diabetes mellitus were examined in a 4-week, randomized, double-blind, placebo-controlled, parallel-group trial. Pramlintide was administered subcutaneously prior to meals in four dosing regimens: 30 microg four times per day (breakfast, lunch, dinner, and evening snack), 30 microg three times per day (breakfast, lunch and dinner [BLD]), 30 microg three times per day (breakfast, dinner and evening snack [BDS]), and 60 microg twice per day (breakfast and dinner). After 4 weeks of pramlintide 30 microg four times per day administration, there was a statistically significant reduction in the mean 24 h plasma glucose concentration when compared to placebo (-1.4 +/- 0.5 vs 0.3 +/- 0.5 micromol/l, p = 0.009). Serum fructosamine concentrations were reduced 62 +/- 10 micromol/l in the pramlintide 30 mg four times per day group, 43 +/- 7 micromol/l in the pramlintide 30 microg three times per day (BLD) group, 47 +/- 6 micromol/l in the pramlintide 30 microg three times per day (BDS) group, 46 +/- 7 micromol/l in the pramlintide 60 microg twice per day group, and 29 +/- 8 micromol/l by placebo. The incidence of hypoglycaemia was not different in any pramlintide group compared to the placebo group. Nausea, the most frequent adverse event, subsided after the first week of treatment in the majority of patients. In conclusion, pramlintide improved blood glucose control over a 4-week period without increased hypoglycaemia and was well tolerated. Future studies using a longer period of pramlintide administration with assessment of HbA1c as the measurement of glycaemic control are warranted.
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PMID:Effects of 4 weeks' administration of pramlintide, a human amylin analogue, on glycaemia control in patients with IDDM: effects on plasma glucose profiles and serum fructosamine concentrations. 938 19

Reovirus type 2 (Reo-2) infection in DBA/1 sucking mice causes pancreatic islet-cell destruction, which results in a diabetes-like syndrome. To investigate the role of reactive oxygen species (ROS), the protective effect of dimethylthiourea (DMTU) was examined, this substance being an effective scavenger of hydroxyl radicals. The degree of cellular infiltration in and around pancreatic islets was the same in mice receiving either virus only or virus and DMTU. The latter had no effect on (1) the number or type of white blood cells, (2) lymphocyte function-associated antigen 1-alpha-positive splenocytes, or (3) viral multiplication in the pancreas. However, treatment with DMTU inhibited the elevation of blood glucose concentrations and reduced pancreatic islet-cell damage (beta-cell degranulation and necrosis). These results suggest that ROS play a role in the pathogenesis of Reo-2-induced diabetes-like syndrome.
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PMID:Dimethylthiourea reduces pancreatic islet-cell damage in DBA/1 sucking mice with reovirus type-2 infection. 950 69

We investigated the therapeutic effects of OK432 (picibanil; CAS39325-1-4), an immunomodulator that is derived from the Su strain of Streptococcus pyogenes. This agent was administered alone or combined with human interferon-alpha in a murine model of insulin-dependent diabetes mellitus. Interferon-alpha inhibits viral replication, reducing the incidence of virus-induced IDDM. Groups of DBA/2 mice (N = 25 per group) received an intraperitoneal injection of OK432 and interferon-alpha daily for 16 d beginning 1 d after inoculation with 500 plaque-forming units of encephalomyocarditis virus (EMCV). The dose of OK432 was one clinical unit (corresponding to 0.1 mg dried cells) per mouse, and that of interferon-alpha was 1 x 10(4) u/g. The animals were killed at random at 3 or 7 d after inoculation with EMCV. The survival rate of mice treated with the combination of OK432 and with interferon-alpha was significantly greater than that of the non-treated infected control animals (P < 0.01). Fasting levels of blood glucose were significantly lower in the mice administered the combination, than in the controls, both on day 3 (68 +/- 21 mg/dl vs. 270 +/- 135 mg/dl, P < 0.01) and on day 7 (101 +/- 29 mg/dl vs. 219 +/- 112 mg/dl, P < 0.01). Serum levels of insulin were significantly higher in the treated mice than in the controls (65 +/- 5 vs. 55 +/- 1 microU/ml, P < 0.05). However, in the mice treated with OK432 or interferon-alpha alone, the survival rate and the blood level of glucose and insulin did not differ from those of infected controls. Natural killer (NK) cell activity was significantly higher in the mice treated with the drug combination than in the controls on both days evaluated: day 3, 65 +/- 5 vs. 55 +/- 1%, n = 3, P < 0.05; day 7, 44 +/- 3 vs. 22 +/- 8%, n = 3, P < 0.05). Serum levels of murine interferon in the treated mice exceeded those in controls on both days evaluated (day 3, 671 U/ml vs. 442 U/ml; day 7, 57 U/ml vs. 43 U/ml). There were no significant differences in NK cell activity or in the interferon level in mice treated with either OK432 or interferon-alpha alone as compared with the infected, non-treated controls. Results suggest that the combination of OK432 and interferon-alpha protects against virally induced IDDM by increasing the activity of NK cells as well as the plasma level of interferon.
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PMID:Combination of OK432 and human interferon-alpha for treating viral-induced diabetes mellitus in mice. 954

We test for the contribution of five strong candidate genes for obesity to quantitative variation for fatness in mice. The candidate loci are known through their major mutant phenotypes. We propose a randomization test for overall contribution of candidate genes, based on the empirical distribution of LOD scores from a quantitative trait locus (QTL) genome scan. The test is applied to data on body fat content and male gonadal fatpad weight from a QTL genome scan with an F2 population of C57BL/6J and DBA/2J inbred mice. The test is nonsignificant in this experiment for overall body fat content. QTLs detected at an experiment-wide significance level on chromosome 4, 6, 13 and 15 have effects on mean fatness of up to 19% between the homozygotes, but map to locations where there is no strong candidate gene. The test is significant for gonadal fat pad weight in males, and gives weak support for an association with the diabetes gene.
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PMID:Test of candidate gene--quantitative trait locus association applied to fatness in mice. 988 88

Reovirus type 2 (Reo-2) infection in DBA/1 suckling mice causes insulitis, which leads to pancreatic islet-cell destruction, resulting in a diabetes-like syndrome. T-helper (Th) 1 cytokines are thought to play a key role in islet inflammation in insulin-dependent diabetes mellitus. We examined this hypothesis in the Reo-2-induced diabetes-like syndrome. We used reverse transcriptase polymerase chain reaction (PCR) and quantitative PCR techniques to examine mRNA expression of interferon (IFN)-gamma (Th1 type cytokine), and interleukin (IL)-4 (Th2 type cytokine) in splenic cells. We observed that in Reo-2 infected mice the level of IFN-gamma expression increases with the development of insulitis, whereas expression of message for IL-4 is minimal to detectable with the immuno-inflammatory process 10 days after infection. The treatment of monoclonal antibody (mAb) against mouse IFN-gamma during the expansion phase of insulitis (5-9 days after infection) inhibited the development of insulitis and the elevation of blood glucose concentrations in a dose dependent manner. Furthermore altered CD4+/CD8+ cell ratio compared with uninfected mice in the splenic cells by the infection was recovered to the ratio of uninfected mice by the treatment of mAb against mouse IFN-gamma, suggesting normalization of T cell balance in immune system. These results suggest that Reo-2-triggered autoimmune insulitis may be mediated by Th1 lymphocytes and IFN-gamma may play a role in islet inflammation leading to islet cell destruction.
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PMID:Interferon-gamma plays a role in pancreatic islet-cell destruction of reovirus type 2-induced diabetes-like syndrome in DBA/1 suckling mice. 1019 14

Reovirus type 2 (Reo-2)-infected DBA/1 suckling mice develop insulitis, resulting in a diabetes-like syndrome. In this study, the role of interleukin-2 (IL-2) in the death (destruction) of pancreatic islet cells was examined. The endogenous IL-2 activity of splenic cells in infected mice was greater than that in uninfected mice. Treatment of infected mice with monoclonal antibody against IL-2 prevented the development of insulitis with impaired glucose tolerance, in a dose-dependent manner. These results suggest that IL-2 may participate in pancreatic islet-cell destruction in Reo-2-induced diabetes-like syndrome.
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PMID:Role of interleukin-2 in pancreatic islet-cell destruction in reovirus type 2-infected DBA/1 suckling mice. 1021 76


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