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

We have previously reported that a single injection of complete Freund's adjuvant (CFA) can prevent diabetes appearance in diabetes-prone (DP) BB rats. In this study, we investigated further the mechanism of CFA-induced protection from diabetes. We found that adoptive transfer of splenic cells from CFA-treated DP rats into young DP rats protected the latter from diabetes development. This suggested that CFA-induced protection from diabetes resulted from activation of regulatory (suppressor) cells. Cell mixing experiments in vitro indicated that CFA activated splenic cells with antigen-nonspecific suppressor activity (suppression of lymphoproliferative responses to lipopolysaccharide and to allogeneic splenic cells). Fractionation of splenic cells on Percoll revealed that the suppressor activity resided in low density cells relatively depleted of T-cells, B-cells, macrophages and NK cells. These results suggest that non-specific (natural) suppressor cells in CFA-treated BB rats may be responsible for suppressing autoimmune responses and preventing insulitis and diabetes development.
 ...
PMID:Mechanisms of complete Freund's adjuvant protection against diabetes in BB rats: induction of non-specific suppressor cells. 134 67

The Bio-Breeding (BB) rat develops spontaneous insulin-dependent diabetes mellitus (IDDM) and provides a useful animal model to study this human autoimmune disease. Treatment of BB rats with tumor necrosis factor (TNF) has been reported to prevent the development of IDDM. This suggests that deficient TNF production may be involved in the immunopathogenesis of autoimmune diabetes. In this study, we evaluated TNF production in diabetes-resistant (DR) BB rats, diabetes-prone (DP) BB rats, and DP BB rats protected from diabetes by the immunoadjuvant, complete Freund's adjuvant (CFA). TNF production in short-term cultures of peritoneal macrophages from DP rats was significantly less than that from control DR rats, both in the basal state and after stimulation with either interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS) in vivo and in vitro. In contrast, TNF production by macrophages from CFA-injected DP rats (basal and IFN-gamma or LPS-stimulated) was equal to or greater than that by macrophages from DP rats and similar to TNF production by macrophages from CFA-injected DR rats. These results suggest that development of autoimmune diabetes in BB rats may be causally related to deficient macrophage production of TNF, and that upregulation of TNF production may protect against diabetes development.
 ...
PMID:Tumor necrosis factor production is deficient in diabetes-prone BB rats and can be corrected by complete Freund's adjuvant: a possible immunoregulatory role of tumor necrosis factor in the prevention of diabetes. 139 29

A panel of CD4+ T-cell clones has been isolated from the spleen and lymph nodes of diabetic NOD mice. These clones have been shown to be islet-specific both in vivo and in vitro. One of the clones, BDC-6.9, initiates extensive damage to islet tissue when placed adjacent to an NOD islet graft that has been used to reverse diabetes in (CBA x NOD)F1 recipients or when injected intraperitoneally into such animals. In this study, we show that BDC-6.9 T cells can initiate islet destruction in the absence of detectable CD8 T cells either in the periphery or in the lesion that develops after the transfer of the cloned islet-reactive T cells.
Diabetes 1992 Dec
PMID:CD8 T cells are not required for islet destruction induced by a CD4+ islet-specific T-cell clone. 144 2

Based on our new finding that an inflammation in which tumor necrosis factor (TNF) is primed or triggered (ontogenic inflammation) can regulate the homeostasis in ontogenesis, we have identified a new lipopolysaccharide from wheat flour (LPSw) that can induce ontogenic inflammation in adult mice. LPSw can prime adult mice to produce TNF when given orally or percutaneously, suggesting that it may maintain homeostasis in adults. LPSw can cure experimental animals of diabetes, hyperlipidemia, ulcer, and herpes. It can also stimulate bone resorption and egg-laying, and shows a strong analgesic effect that is blocked by naloxone. This effect even allows a release from drug addiction. Suppression of serum cholesterol level by oral uptake of LPSw in Watanabe heritable hyperlipidemic (WHHL) rabbit was also observed. Infection of toxoplasma was prevented by oral uptake of LPSw. The realization that a single oral or percutaneous administration of LPSw may be a cure for multiple intractable diseases may lead to the presentation of a nontoxic type of Coley's toxin, which is known to be an efficient cancer treatment, but has high toxicity.
 ...
PMID:Oral or percutaneous administration of lipopolysaccharide of small molecular size may cure various intractable diseases: a new version of Coley's toxin. 147 70

We have recently reported that chronic and systemic administration of tumor necrosis factor alpha (TNF) inhibits development of autoimmune diabetes in NOD mice and BB rats, animal models of insulin-dependent diabetes mellitus (IDDM). During these experiments, we unexpectedly found that in vivo production of TNF stimulated by a single injection of lipopolysaccharide was enhanced approximately 10 times in the long-term diabetic BB rats (P less than 0.0001), whose mean duration of diabetes with more than 16.8 mM (300 mg/dl) of nonfasting blood glucose level was 26.2 +/- 2.1 days, as compared to that in the rats of nondiabetes and in the rats at the onset of diabetes, whose mean duration of diabetes was 1.4 +/- 0.6 days. The long-term diabetic, but not short-term-diabetic, rats were also associated with increased levels of serum fructosamine/albumin (P less than 0.01) and triglyceride (P less than 0.01) and with a decreased level of serum albumin (P less than 0.01). The in vivo TNF productivity in the diabetic rats, including the short-term- and long-term-diabetic rats, was correlated positively with the level of fructosamine/albumin (P less than 0.05) and negatively with the level of serum albumin (P less than 0.05), but not with levels of blood glucose. None of these correlations were observed in nondiabetic rats. The increased LPS-induced serum TNF activity in the long-term diabetic state was observed not only in BB rats but also in NOD mice and GK rats, a model of non-IDDM, irrespective of sexes and ages, indicating that the enhancement of in vivo TNF production was a result of long-term diabetes. These findings indicate that some factor(s) associated with the long-term-diabetic state may prime macrophages in vivo to produce TNF. Further study is needed to reveal a mechanism of the enhanced TNF production and its possible relevance to various abnormalities associated with the chronic hyperglycemic state.
 ...
PMID:Increased in vivo production of tumor necrosis factor after development of diabetes in nontreated, long-term diabetic BB rats. 154 Oct 51

The expression of adhesion molecules in monocytes of patients with recent onset type I diabetes was analysed. Monocytes were identified as CD14-positive cells by flow cytometry. The percentage of monocytes expression LFA-1 alpha, ICAM-1 and HLA-DR was slightly lower in recent onset type I diabetes (n = 13) compared to normal subjects (n = 15) and was significantly decreased after activation of cells with lipopolysaccharide and interferon-gamma for 5-24 hr. Receptor densities on adhesion molecule-positive monocytes and the expression of LFA-1 beta were normal. These data indicate that monocyte trafficking is abnormal in recent onset type 1 diabetes.
 ...
PMID:Decreased expression of adhesion molecules on monocytes in recent onset IDDM. 167

We have recently reported that systemic and chronic administration of recombinant tumour necrosis factor alpha (TNF-alpha), as well as streptococcal preparation (OK-432), inhibits development of insulin-dependent diabetes mellitus (IDDM) in NOD mice and BB rats, models of IDDM. In this study we examined whether serum containing endogenous TNF induced by OK-432 injection could inhibit IDDM in NOD mice. Treatment twice a week from 4 weeks of age with OK-432-injected mouse serum, which contained endogenous TNF (75U), but not IL-1, IL-2 and interferon-gamma (IFN-gamma) activity, reduced the intensity of insulitis and significantly inhibited the cumulative incidence of diabetes by 28 weeks of age in NOD mice, as compared with the incidence in non-treated mice (P less than 0.01) and in mice treated with control serum (P less than 0.02). This inhibitory effect of the serum was diminished, although not significantly, by neutralization of serum TNF activity with anti-mouse TNF antibody. In the mice treated with the serum from OK-432-injected mice, Thy-1.2+ or CD8+ spleen cells decreased (P less than 0.01) and surface-Ig+ (S-Ig+) cells increased (P less than 0.05), whereas the proliferative response of spleen cells to concanavalin A (P less than 0.01) and lipopolysaccharide (P less than 0.05) increased. The results indicate that the inhibition by OK-432 treatment of IDDM in NOD mice was partially mediated by serum factors including endogenous TNF.
 ...
PMID:Inhibition of autoimmune diabetes in NOD mice with serum from streptococcal preparation (OK-432)-injected mice. 174 49

BDC-6.9 is a CD4-positive T-cell clone, specific for NOD islets, which was isolated from the spleen and lymph nodes of a diabetic NOD mouse. The cells were transplanted in a blood clot adjacent to established NOD islet grafts in diabetic (CBA X NOD)F1 recipients. The BDC-6.9 cells initiated extensive damage to the islet grafts, while a non-islet specific clone transplanted adjacent to grafted islets caused no noticeable damage. In addition, the BDC-6.9 cells initiated similar destruction when injected intraperitoneally, suggesting that they may have some migratory capacity. By introducing these islet-reactive cells into the (CBA X NOD)F1, a non-diabetes prone environment, we hope to clarify the role of the islet-specific CD4 cell as related to islet destruction in vivo.
 ...
PMID:In vivo activity of an islet-reactive T-cell clone. 197 4

Rat neutrophil chemotactic responses to N-formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene (LT) B4, and lipopolysaccharide-activated serum (LPS-AS) were quantitatively assessed using the micropore filter system. Cells were suspended in either normal or diabetic rat serum for testing. Diabetic donor serum did not affect migration of neutrophils in a concentration gradient of the synthetic chemotactic agents. In contrast, the migratory responses to LPS-AS were significantly less than normal in this circumstance. Summation of effects was observed when FMLP and LPS-AS, or LTB4 and LPS-AS were simultaneously added to the test chamber, with cells suspended in normal serum. Suspended in diabetic rat serum neutrophils responded normally to the synthetic chemoattractants but the response to the activated serum was blocked. Cells previously incubated in the presence of diabetic donor serum then transferred to a culture medium for testing, presented reduced migratory responses to LPS-AS. Supramaximal, inhibitory concentrations of FMLP and LTB4, did not influence the response of neutrophils to LPS-AS. In vivo, suppression of cellular emigration to an inflamed area was observed from the early stages of the diabetic state. The inhibitory activity of chemotaxis in diabetes mellitus was previously reported to be associated with a protein factor in plasma of the animals. It is suggested that the inhibitory factor of chemotaxis in diabetes mellitus interacts with neutrophil receptors for complement-derived chemoattractants to induce blockade of cell-oriented locomotion either in vitro or in vivo.
 ...
PMID:Inhibition of leukocyte chemotaxis by serum factor in diabetes mellitus: selective depression of cell responses mediated by complement-derived chemoattractants. 216 2

The effect of cyclosporin (CsA) on the endotoxin-induced generalized Shwartzman reaction (GSR) was studied in diabetic and nondiabetic rats. After 4.5 wk of diabetes, CsA (20 mg/kg) or intralipid as a control substance was given intraperitoneally daily for 10 days. Next, diabetic rats were given either high-dose (2 mg/kg or low-dose (0.1 mg/kg) endotoxin (Escherichia coli 026:B6 lipopolysaccharide B) as a single injection. The rats were killed at intervals of 1, 4, 8, and 24 h. No significant glomerular thrombi were seen in the nondiabetic control animals, whereas the severity of glomerular thrombi in the diabetic animals was dependent on the presence or absence of CsA, endotoxin dose, and degree of glycemic control. In the diabetic rats, glomerular thrombi occurred maximally at 4 h but were no longer present at 24 h. The CsA/high-dose-endotoxin rats had fewer glomerular thrombi than rats receiving the intralipid/high-dose endotoxin, but this difference was not statistically significant. The CsA/low-dose-endotoxin rats had increased glomerular thrombi compared with the intralipid/low-dose-endotoxin rats (P less than 0.01). Insulin treatment reduced the glomerular capillary thrombi in the CsA/low-dose-endotoxin diabetic animals. Thus, CsA aggravates the GSR with low-dose endotoxin but has no significant effect when high-dose endotoxin is given. Improved glycemic control reduces the GSR in CsA-treated rats. Thus, the interrelationships of diabetes, endotoxin, and CsA on the GSR are complex, and the pathogenesis of these events is unclear.
Diabetes 1990 Jan
PMID:Effect of cyclosporin on generalized Shwartzman reaction in diabetic rats. 221 64


1 2 3 4 5 6 7 8 9 10 Next >>