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

A 5-day culture of adult rat islets with human recombinant IL-1 beta (3 U/ml) resulted in the death of most alpha-cells and 50% of beta-cells. The IL-1--exposed islet tissue contained--in addition to poorly granulated beta-cells--patches of outgrowing monolayers and dispersed activated macrophages. In purified alpha- and beta-cell preparations, no cytodestructive effects of IL-1 (as high as 30 U/ml) were noticed, indicating that the cytokine is in itself not a beta-cell--selective killer. Pure beta-cells were, on the other hand, more sensitive (from 0.3 U/ml on) than intact islets to an IL-1--induced suppression of hormone synthesis. This inhibitory action was reversible and affected predominantly the production of insulin, leading to degranulated cells with modified shape and attachment. Further studies with IL-1 should take into account that isolated islet preparations do not allow distinction between its irreversible, indirect, and aspecific beta-cell toxicity and its reversible, direct, and specific suppression of beta-cell functions. It is not yet known whether IL-1--suppressed beta-cells exhibit an altered sensitivity to beta-cell--toxic conditions.
Diabetes 1993 Jan
PMID:Interaction of interleukin-1 with islet beta-cells. Distinction between indirect, aspecific cytotoxicity and direct, specific functional suppression. 842 Aug 20

NO has been identified recently as the prime islet-toxic product of inflammatory macrophages. The adverse effects of IL-1 on isolated islets also have been reported to involve NO. We now show that exposure of an islet cell suspension to the NO donor nitroprusside or to activated macrophages leads to DNA strand breaks. Macrophages did not induce DNA damage in the presence of the NO synthase inhibitor NG-methyl-L-arginine. DNA strand breaks were demonstrated at the level of single cells by a modified nick-translation procedure and confirmed by analysis of DNA fragmentation by gel electrophoresis. DNA strand breaks occurred within 1 h and preceded islet cell lysis. DNA damage could not be prevented by inhibitors of endogenous endonucleases. We conclude that islet cell DNA is an early target of NO action.
Diabetes 1993 Mar
PMID:Islet cell DNA is a target of inflammatory attack by nitric oxide. 843 20

Several lines of evidence point to abnormalities of the phenotype, cytokine responses, and function of cells of the myeloid lineage in non-obese diabetic (NOD) mice. In this study we have characterized the phenotype and myeloid progenitor function of NOD bone marrow. Two hematopoietic differentiation antigens, Ly-6C and AA4.1, are expressed abnormally on NOD bone marrow cells. While multilineage erythromyeloid progenitor cells (day 12 CFU-S) are normal in number in NOD mice, more differentiated myeloid progenitors are deficient in their in vitro responses to IL-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), and IL-5. Since the diabetes-predisposing Idd-5 gene of NOD mice maps close to the IL-1 receptor, we tested NOD bone marrow cells for a defect in synergy between IL-1 and IL-3; no defect was found. The defects in myelopoiesis described here may predispose the NOD mouse to autoimmunity by impairing macrophage maturation.
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PMID:Bone marrow abnormalities in the non-obese diabetic mouse. 845 15

Dendritic cells (DC) present antigen and initiate T cell-mediated immune responses. To investigate the possible association of autoimmunity with DC function, we compared the accessory activity of splenic DC from Wistar/Furth (WF) and diabetes-prone (DP) BioBreeding (BB) rats. The latter develop autoimmune diabetes and thyroiditis. DC function was quantified in vitro by measuring T cell proliferation in mitogen-stimulated and mixed lymphocyte reactions. When purified without macrophage coculture, WF and DP DC displayed similar levels of accessory activity. In contrast, when purified by a method involving coculture with macrophages, DC from DP rats consistently displayed greater accessory activity. This finding could not be explained by morphological or phenotypic differences between DP and WF DC. In accessory activity assays performed after reciprocal DC cocultures with DP and WF macrophages, DP DC exhibited higher accessory activity irrespective of macrophage donor strain. We also compared the accessory activity of WF and DP DC cultured in the presence of conditioned medium and a mixture of IL-1 and GM-CSF. In all assays, DP DC exhibited higher accessory activity. In studies of (WF x DP) F1 hybrids, the high accessory activity of DP DC was observed to be heritable, and studies of WF and DP radiation chimeras indicated that the effect was an intrinsic property of the DP hematopoietic system. We conclude: (a) splenic DC from DP and WF rats possess similar basal levels of accessory potency; (b) after interaction with macrophages, DC of DP origin are capable of greater stimulatory activity than are WF DC; and (c) the mechanism responsible for this phenomenon involves differential responsiveness of DP and WF DC to macrophage-derived factors such as IL-1 and GM-CSF.
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PMID:High stimulatory activity of dendritic cells from diabetes-prone BioBreeding/Worcester rats exposed to macrophage-derived factors. 848 73

In order to evaluate the influence of hyperlipemia on the specific cell defence reaction in type-II diabetes mellitus in humans, 20 diabetics were recruited in this study. They were divided into two groups on the basis of the absence or coexistence of abnormal serum lipid pattern. The lymphocyte and monocyte cells drawn from the type-II diabetic patients with abnormally elevated serum levels of cholesterol and triglycerides showed a decreased expression of major histocompatibility complex (MHC) class-II antigens and an impaired secretion of interleukin (IL-1). Values of MHC class-II antigen expression in diabetics without lipid metabolic alterations were not significantly different from those found in healthy subjects. In conclusion, abnormalities of lipid metabolism often found in type-II diabetes mellitus may play a key role in the impaired specific cell reaction toward infectious diseases of these patients.
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PMID:HLA class II antigens and interleukin-1 in patients affected by type-II diabetes mellitus and hyperlipemia. 850 2

Cytokines, particularly interleukin 1 (IL-1) and tumor necrosis factor, are known to induce hypoglycemia in normal rodents or different experimental models of type II diabetes. We investigated, at the pre-diabetic stage, the effect of short-term administration of murine recombinant interleukin-1 alpha (mrIL-1 alpha) on the levels of glucose, insulin and corticosterone in the non-obese diabetic (NOD) mouse, a spontaneous model of type I diabetes. Two-month-old, pre-diabetic NOD mice of both sexes were insensitive to mrIL-1 alpha (12.5 and 50 micrograms/kg) 2 h after administration, the time at which the maximal decrease (around 50%) was observed in the C57BL/6 mouse strain. Kinetic studies however showed that mrIL-1 alpha lowered glycemia in both sexes of NOD mice, but the effect was limited and delayed. In the NOD and C57BL/6 strains, mrIL-1 alpha had no influence on insulin levels in females, but significantly increased them in males (P < 0.0001). Castration of NOD males abrogated the stimulatory effect of mrIL-1 alpha on insulin secretion. Corticosterone secretion was stimulated by mrIL-1 alpha in both sexes of NOD and C57BL/6 mice, and this effect was faster and greater in NOD females than in C57BL/6 females. The incomplete hypoglycemic response to mrIL-1 alpha in females may be attributed to the anti-insulin effect of glucocorticoids, an effect which can be demonstrated when mrIL-1 alpha is administered to adrenalectomized animals or when mrIL-1 alpha is administered together with the glucocorticoid antagonist RU38486. In NOD males, in contrast, glucocorticoids did not play a major role in the limited hypoglycemic response to mrIL-1 alpha, since RU38486 and adrenalectomy were not able to unmask a hypoglycemic effect. Moreover, NOD mice of both sexes were less sensitive than C57BL/6 mice to the hypoglycemic effect of insulin (2.5 U/kg), which suggests some degree of insulin-resistance in NOD mice. With regard to the effect of IL-1 on NOD mouse glycemia, therefore, these results suggest that glucocorticoids and/or androgens, according to the animal's sex, may induce a state of insulin-resistance.
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PMID:Interleukin-1 effect on glycemia in the non-obese diabetic mouse at the pre-diabetic stage. 856 61

Microencapsulated pancreatic Langerhans islets in calcium alginate gels have been used as an implantable bio-artificial pancreas in the treatment of diabetes mellitus, but with limited success due to overgrowth of the capsule with fibroblasts and phagocytes. The authors earlier demonstrated that alginates enriched in mannuronic acid stimulate human monocytes to produce high levels of cytokines such as tumour necrosis factor (TNF), IL-1 IL-6. In this study the authors have measured the TNF production from peripheral blood mononuclear cells (PBMC) in different groups of insulin-dependent diabetes mellitus (IDDM) patients after stimulation with different alginates and lipopolysaccharide (LPS). It was found that high G-alginate did not induce TNF production in any of the groups. High-M alginate and LPS induced a dose-dependent TNF production in all groups and the production was significantly different from unstimulated cells. The highest TNF response was found in newly diagnosed IDDM patients and the lowest was in the controls.
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PMID:TNF production from peripheral blood mononuclear cells in diabetic patients after stimulation with alginate and lipopolysaccharide. 860 69

The paper presents the molecular biology and biological activity of IL-1 alpha, IL-1 beta and IL-1 receptor antagonist. The role of IL-1 family in pathogenesis of a various disease including myeloid leukemias and other neoplastic diseases, diabetes mellitus, inflammatory diseases, sepsis syndrome and atherosclerosis is presented. Potential therapeutic value of IL-1 and IL-1 receptor antagonist is also discussed.
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PMID:[Biological properties and clinical importance of interleukin 1]. 865 31

The macrophage-derived cytokine, interleukin-1 beta (IL-1 beta), has been implicated to play an important role in the autoimmune beta cell lesion of insulin-dependent diabetes mellitus (IDDM) because of its inhibition of insulin secretion, direct cytotoxicity, and alteration of islet cell antigen expression. Because transforming growth factor beta (TGF-beta) has been reported to inhibit IL-1 receptor expression in several lymphoid and progenitor cell lines, to induce IL-1 receptor antagonist protein (IRAP) production in human peripheral blood monocytes, and to antagonize several effects of inflammatory cytokines and because oral tolerance may be mediated in part by TGF-beta released by regulatory T lymphocytes, we investigated whether TGF-beta counteracted the effects of IL-1 beta on islet cells. Islets isolated from Sprague-Dawley rats were cultured with or without recombinant human IL-1 beta and TGF-beta. Accumulated insulin secretion, cytokine-induced cytotoxicity, and islet cell expression of glutamic acid decarboxylase 65 (GAD-65) and heat-shock protein 70 (HSP-70) were measured in this study. We found that (1) IL-1 beta at 50 and 100 pg/ml inhibited insulin secretion by 41.9 +/- 14.8 and 52.6 +/- 3.5% and induced cytotoxicity by 46.5 +/- 17.3 and 54.1 +/- 6.1%, respectively. IL-1 beta at 1000 pg/ml significantly increased HSP-70 expression and decreased GAD-65 expression. (2) TGF-beta at 0.1, 1, 10, and 40 ng/ml had no significant effect on insulin secretion and did not induce cytotoxicity, TGF-beta at 40 ng/ml had no effect on the expression of either HSP-70 or GAD-65. (3) In combination, TGF-beta at 1, 10, and 40 ng/ml did not antagonize the IL-1 beta (50 and 100 pg/ml)-induced inhibition of insulin secretion or cytotoxicity; TGF-beta (40 ng/ml) did not block the effects of IL-1 beta (1000 pg/ml) on HSP-70 or GAD-65 expression. In conclusion, recombinant human TGF-beta does not counteract these effects of recombinant human IL-1 beta on rat pancreatic islet cells.
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PMID:Recombinant human transforming growth factor beta does not inhibit the effects of interleukin-1 beta on pancreatic islet cells. 874 89

Several data suggest that the endocrine and immune systems are closely interconnected, therefore, we investigated the effect of interleukin-1 on adrenocortical regeneration. The study was performed on adult rats subjected to left adrenal enucleation combined with contralateral adrenalectomy. The animals were given purified human recombinant IL-1 alpha (5 micrograms/kg), IL-1 beta (5 micrograms/kg) anti-human IL-1 receptor antibody (10 micrograms/kg) and combination of interleukins and antibodies. The cell proliferation measured by bromodeoxyuridine incorporation and plasma corticosterone determined by a RIA kit were evaluated six days after operation. The mean cell growth ratio expressed as number of BrdU-positive cells per 1,000 cells was 11.86 +/- 0.45 in the control group. IL-1b significantly stimulated the proliferation ratio (15.30 +/- 0.88; p < 0.01) and this effect could be prevented by addition of IL-1rAb. The antibody caused also a well-marked inhibition of cell growth ratio (8.23 +/- 0.67; p < 0.01). The plasma corticosterone concentration was higher in IL-1b-treated animals than in the control group, 107.79 +/- 2.82 vs. 61.08 +/- 2.0 ng/ml, respectively, p < 0.01. On the other hand, IL-1rAb decreased corticosterone secretion (31.53 +/- 2.58 ng/ml, p < 0.01) and reversed the stimulatory effect of of IL-1b. In contrast, IL-1a seemed to have no influence on adrenocortical regeneration. In conclusion, this study supported the thesis of close interconnection between immune and endocrine systems and revealed that IL-1b could act as a growth-promoting factor on regenerating adrenal cortex in the rat.
Exp Clin Endocrinol Diabetes 1995
PMID:Effect of interleukin-1a, IL-1b and IL-1 receptor antibody on the proliferation and steroidogenesis of regenerating rat adrenal cortex. 878 10


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