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

The function of clonal insulin-secreting RINm5F cells was compared with parent tumoural B-cells from radiation-induced NEDH rat insulinoma and a RINm5Fr cell line established following transplantation of RINm5F cells in NEDH rat. After 3 days culture, tumoural B-cells contained 156 micrograms insulin/10(6) cells and released 57-82 ng insulin/10(6) cells/h during acute incubations at 2.6 mM Ca2+. RINm5F cells contained 0.56 ng insulin/10(6) cells and released 62-181 pg insulin/10(6) cells/h. Unlike tumoural B-cells, secretion was stimulated 1.7-2.4-fold by 5 mM theophylline, 1 microM glucagon, 25 mM K+, or 7.6 mM Ca2+. Subscapular transplantation of cultured tumoural B-cells or RINm5F cells (2.8 X 10(7) cells/rat) resulted in an encapsulated tumour associated with progressive hyperinsulinaemia, hypoglycaemia and death by 28-46 days and 39-44 days respectively. A RINm5Fr cell line was established in culture from a 19 g tumour 20 days after transplantation. RINm5Fr cells contained 2.69 ng insulin/10(6) cells and released 385-1,017 pg insulin/10(6) cells/h (p less than 0.001 compared with RINm5F cells). Secretion was not augmented by glucose, but at 16.7 mM glucose it was stimulated 1.5-fold by 5 mM theophylline, 1.6-fold by 1 microM glucagon and inhibited 0.6-fold by somatostatin. At 5.6 mM glucose, secretion was stimulated 1.6-fold by 25 mM K+, 2.5-fold by 7.8 mM Ca2+, 2.1-fold by 20 microM A23187, 1.5-fold by 20 mM leucine and 1.4-fold by 100 microM tolbutamide. These data indicate fundamental differences between rat insulinoma cells and the derived RIN cell lines. Transplantation is a useful means to enhance the function of RINm5F cells.
Diabetes Res 1987 Oct
PMID:Insulin secretion in vivo and in vitro from transplantable NEDH rat insulinoma and derived clonal RINm5F cell line. 282 34

Insulin-dependent diabetes is a chronic autoimmune disease probably mediated by T cells. We examined the alpha chain of the T-cell antigen receptor in two models of this illness (man and BB rat) to determine any association with autoimmune diabetes. We conducted a population study in man, using a human alpha chain probe, pGA-5, and restriction enzyme Bgl 11. Two allelic forms and three RFLP patterns, 2.8 and 3.0 kb homozygous and 2.8/3.0 heterozygous, were detected. There was no difference in the frequency of these RFLPs among the 50 Type I diabetic patients and 48 controls tested. BB rats develop a spontaneous T-cell mediated autoimmune diabetes. The diabetes has been linked in several breeding studies to an undetermined autosomal recessive gene causing T-cell lymphopenia. We were able to differentiate the T-cell antigen receptor alpha chain of the diabetic BB and control BBN rats using the restriction enzyme EcoR1 and a murine alpha chain probe, TT11. The BB rat had a haplotype characterized by the presence of 4.7 and 5.8 kb bands, and the absence of 1.4, 2.2, 2.6, 3.6, 3.9, 4.1, and 6.1 kb bands. In a breeding study with BB and BBN rats, diabetic animals of the F2 generation demonstrated no linkage with the BBs' alpha chain, nor was lymphopenia linked to the alpha chain of the BB rat. These results suggest that autoimmune diabetes is not linked to the T-cell antigen receptor alpha chain in the BB rat, nor is it associated with alpha chain constant region polymorphisms in Type I diabetes in man.
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PMID:T-cell antigen receptor alpha chain polymorphisms in insulin-dependent diabetes. 290 75

Recent developments in transplantation immunobiology, concerning the mechanism of tissue rejection, clearly indicate that antigen recognition alone is not sufficient for lymphocyte activation. "Passenger" leucocytes (antigen presenting cells) carried in the donor tissue are now recognized as the major immunogenic stimulus, such that removal of these contaminating leucocytes, using a variety of procedures, has enabled the immunogenicity of allografts to be reduced and the survival of the graft to be significantly extended. Remarkable advances have been made in recent years in preventing rejection of islet allografts, and even xenografts, in experimental animals by using procedures which do not involve continuous immunosuppressive therapy. Cryopreservation offers not only the means by which donor tissue can be stored effectively during such procedures but also the possibility that, under appropriate conditions, the freezing and thawing process itself could modulate tissue immunogenicity by allowing the selective killing of immunocompetent leucocytes whilst preserving the function of parenchymal cells in the graft. In this preliminary study we have characterized the survival of leucocytes and islets from the same species (rat) after cryopreservation by the same technique using dimethyl sulphoxide (Me2SO) as the cryoprotectant. Optimum survival of rat lymphocytes and macrophages was found at cooling rates in the range of 0.3-5 degrees C/min, after cooling at rates greater than 75 degrees C/min, survival was reduced to a negligible level. On the other hand, recovery of islets was 73 +/- 9% at 75 degrees C/min, indicating that depletion of lymphoid cells, with satisfactory preservation of endocrine cells, should be obtainable at this cooling rate.
Diabetes Res 1987 Jun
PMID:Selective killing of leucocytes by freezing: potential for reducing the immunogenicity of pancreatic islets. 311 61

This is the first study concerning the extent to which relative collagen production (RCP) in rat periodontal tissues is affected by diabetes. Determination of RCP, rather than individual production rates for collagen or for non-collagen protein, was deemed necessary because saturation of all proline pools in tissues of diabetics (and non-diabetic controls) was not achieved. Such non-saturation occurred despite the injection of a pool-expanding dose of proline (400-1150 mg/rat), non-saturation indicated by the lesser specific radioactivity (S.R.) of free-[3H]proline in tissues than that of the injected solution. RCP was decreased in five periodontal tissues (incisor and molar gingiva, incisor and molar periodontal ligament, antemolar palatal mucosa) and in skin. Diabetes-decreased RCP seems to result from decreased collagen synthesis and increased intracellular degradation, although some evidence is presented for increased extracellular degradation of recently secreted collagen.
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PMID:Streptozotocin-induced diabetes and the rat periodontium: decreased relative collagen production. 339 6

The regulation of nonshivering thermogenesis by insulin was studied in cold-acclimated rats (2 weeks at 5 degrees C) made diabetic after injection with streptozotocin (75 mg/kg, i.p.) and maintained in the warm (25 degrees C) for 2-7 days. To investigate whether thermogenesis was activated in brown adipose tissue (BAT) of diabetic rats under physiological conditions, conscious rats were briefly exposed to cold (2 h at 5 degrees C) and the temperature of interscapular BAT (Tbat) was compared with the colonic temperature (Tcol). It was found that Tbat, Tcol, and Tbat-Tcol (an index of thermogenesis activation in BAT) were significantly reduced in 7-day diabetic rats (P less than 0.01) but not in 2-day diabetic animals, suggesting that diabetes progressively decreases BAT thermogenic capacity. To further assess whether the maximal capacity of BAT for nonshivering thermogenesis was affected by the lack of insulin, the calorigenic response to noradrenaline (0.4 mg/kg, i.m.) was determined at 25 degrees C in anesthetized animals using an open circuit respirometer. The results showed that the calorigenic response to noradrenaline was inhibited by 50 and 70% in 2- and 7-day diabetic rats, respectively. Significantly, tissue weight, protein content, and cytochrome oxidase activity of interscapular BAT were also decreased by 30-40% and 50-70% in the same animals. Insulin treatment of 3-day diabetic rats for 4 days (6.5 U/day per rat) restored their calorigenic response to noradrenaline to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of insulin in nonshivering thermogenesis. 355 63

Increasing evidence that Type 1 (insulin dependent) diabetes mellitus is an autoimmune disease, together with successful cure/prevention in animal models of this disease (e.g. BB/W rat) has led to several trials of immunotherapy in recent onset Type 1 diabetes of man. In this communication we report our experience with short courses of prednisone and antithymocyte globulin (ATGAM) plus prednisone. Prednisone characteristically suppressed Ia positive T lymphocytes into the normal range, but had no long-lasting effect on T-cell phenotype. ATGAM plus prednisone markedly decreased the ratio of T4/T8 ("helper"/"suppressor-cytotoxic") positive T lymphocytes, and this remained suppressed for months. ATGAM treated patients had lower HbA1c on a lower dose of insulin 100 or more days following immune therapy (with 4 out of 5 patients requiring less than 0.2 U/Kg insulin/day). Two patients in the ATGAM treated group did not require insulin for more than 8 months; during remission they had normal fasting blood glucose values, but with abnormal glucose tolerance on oral glucose tolerance testing. Severe, though transient, thrombocytopenia was observed in 2 patients on ATGAM therapy which outweighed its clinical effects.
Diabetes Res 1985 Nov
PMID:Anti-thymocyte globulin and prednisone immunotherapy of recent onset type 1 diabetes mellitus. 387 62

Evidence is accumulating that the development of insulin-dependent diabetes mellitus involves autoimmune phenomena, both in the human and in the BB rat model. A strong association is observed in both cases with alleles of the class II major histocompatibility complex (MHC). Results of the present study show that autoimmune phenomena, as assessed by the presence of clinical diabetes or histological thyroiditis, are prevented by the injection of monoclonal antibodies to class II gene products in the BB rat. Immunosuppression was specifically obtained with a monoclonal antibody to the murine I-E equivalent, as opposed to the murine I-A equivalent, of the rat major histocompatibility complex. This represents indirect evidence for I-E subregion control of immune responses to islet cell and thyroid antigens in the BB rat model. The frequent occurrence of anaphylactic type deaths in young (1 month old) animals receiving more than six weekly injections of partially purified homologous (rat) monoclonal antibodies to rat class II gene products underscores the potential risks of this type of immunotherapy. The presumed immunologic mechanism (IgE antibody) and its specificity (anti-allotype, anti-idiotype, or anti-impurity) must be clarified to assess the risks and feasibility of this type of therapy.
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PMID:In vivo prevention of thyroid and pancreatic autoimmunity in the BB rat by antibody to class II major histocompatibility complex gene products. 390 Oct 5

The effect of oral administration of diazoxide on rats bearing mammary carcinomas induced by dimethylbenzanthracene (7,12-DMBA) or methylnitrosourea (MNU) was investigated. Administration of 300 mg/kg diazoxide caused mild reversible diabetes with maximum glucose levels of 305 +/- 74 (control: 119 +/- 12) mg/dl and related insulin levels of 15 +/- 5 (control: 24 +/- 11) microU/ml after 4 hr in tumor-bearing animals. Following the same dose of diazoxide a more than 90% inhibition of tumor growth was observed in 7,12-DMBA- and MNU-induced autochthonous rat mammary carcinomas as well as remission of the median total tumor volume per group in 7,12-DMBA-induced lesions. Frequently, onset of remissions and median remission duration proved to be dose-dependent in 7,12-DMBA-induced mammary carcinoma and, with the exception of the median remission duration, in MNU-induced tumors too. After cessation of diazoxide application, 30% rebound responses were observed in 7,12-DMBA-induced tumors of animals that had had a first remission due to diazoxide. Application of insulin (2 IU per rat) together with diazoxide (300 mg/kg) reversed the tumor-inhibiting effect of diazoxide in MNU-induced tumors. The diazoxide effect might in part be due to a decrease in the percentage of proliferating cells caused by insulin depletion as indicated by a lower amount of cells in S-phase, as measured by DNA-flow cytometry. Marked toxicity was observed after effective doses of diazoxide; the experiments indicate that induction of reversible diabetes might be a useful tool in the treatment of hormone-dependent mammary carcinoma.
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PMID:Effects of diazoxide-induced reversible diabetes on chemically induced autochthonous mammary carcinomas in Sprague-Dawley rats. 391 48

Congenital malformations now represent the largest single cause of mortality in the infant of the diabetic mother. The mechanism by which diabetes exerts its teratogenic effects is not known. This study evaluated whether arachidonic acid might be involved, a possibility raised by the role of arachidonic acid in palatal elevation and fusion, processes analogous to neural tube folding and fusion. This hypothesis was tested in two animal models of diabetic embryopathy, the in vivo pregnant diabetic rat and the in vitro hyperglycemic mouse embryo culture. The subcutaneous injection of arachidonic acid (200-400 mg/kg per day) into pregnant diabetic rats during the period of organ differentiation (days 6-12) did not alter the maternal glucose concentration, the maternal weight gain, or the weight of the embryos. However, the incidence of neural tube fusion defects was reduced from 11% to 3.8% (P less than 0.005), the frequency of cleft palate was reduced from 11% to 4% (P less than 0.005), and the incidence of micrognathia was reduced from 7% to 0.8% (P less than 0.001). The addition of arachidonic acid to B10.A mouse embryos in culture also resulted in a reversal of hyperglycemia-induced teratogenesis. The teratogenic effect of D-glucose (8 mg/ml) in the medium resulted in normal neural tube fusion in only 32% of the embryos (P less than 0.006 when compared to controls). Arachidonic acid supplementation (1 or 10 micrograms/ml) produced a rate of neural tube fusion (67%) that was not significantly different from that observed in controls. The evidence presented indicates that arachidonic acid supplementation exerts a significant protective effect against the teratogenic action of hyperglycemia in both in vivo (rat) and in vitro (mouse) animal models. These data therefore suggest that the mechanism mediating the teratogenic effect of an increased glucose concentration involves a functional deficiency of arachidonic acid at a critical stage of organogenesis.
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PMID:Hyperglycemia-induced teratogenesis is mediated by a functional deficiency of arachidonic acid. 393 70

The BB rat develops a syndrome of autoimmune diabetes similar to Type I diabetes of man. It also has a severe T cell lymphopenia. As part of an ongoing breeding program to transfer the diabetogenic genes of the BB rat onto inbred rat strain backgrounds, diabetic animals were used in a backcross (BC)- intercross (IC)-backcross breeding scheme with Brown Norway (BN), Lewis (L), and Wistar-Furth (WF) inbred rats. We have used monoclonal antibodies to analyze both lymphopenia and major histocompatibility (MHC) antigens (the RT1 locus in the rat) in relation to the development of diabetes. To examine T cell subsets we used a panel of monoclonal antibodies, in particular W3/25 and OX19 , which discriminate the abnormal phenotype better than W3/13. In our breeding program, at least two independent genes or gene complexes are required for the expression of diabetes. One gene determines the lymphopenia, is inherited by simple autosomal recessive genetics and is not linked to the MHC. The second gene is linked to the MHC. Both genes are necessary, but neither gene is sufficient by itself for the development of diabetes.
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PMID:Two genes required for diabetes in BB rats. Evidence from cyclical intercrosses and backcrosses. 620 17


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