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

Sera from newly diagnosed type I (insulin dependent) diabetic patients and control subjects were tested by indirect immunofluorescence on a particular subclone of RINm5F cells for the presence of cytoplasmic antibodies. Cell cultures after biochemical fixation and frozen sections of cell sheets obtained after incubating confluent monolayers with dispase were used alternatively as substrate. Eight out of ten ICA positive sera previously tested on frozen sections of human pancreas bind RIN cells when fixed with acetone-ethanol whereas no staining was obtained after treating the cells with paraformaldehyde or glutaraldehyde. Four normal sera did not bind RIN cells under these conditions. Alternatively, frozen sections of cell sheets appeared to be a more sensitive substrate as all ICA positive sera tested reacted with cell cytoplasm. In addition, an immunoradiometric assay was developed using microtitre plate wells coated with Nonidet P40 solubilized RIN antigens. Coated wells were incubated with ICA positive and ICA negative diabetic sera along with sera from normal individuals. Antigen antibody complexes were detected by the binding of 125I-Protein A. A good correlation was found between binding values and results obtained by indirect immunofluorescence on frozen sections of human pancreas. Although this study indicates that RIN cells express a specific cytoplasmic antigen to which ICA positive sera bind, more information is required concerning the exact nature of this antigen before such assay can be reliably used for the detection of ICA.
Diabetes Res 1987 Oct
PMID:Human islet cell autoantibodies specifically bind cloned rat islet cells. 332 34

We sought direct evidence for anti-islet cellular cytotoxicity in diabetic Bio-Breeding/Worcester (BB/W) rats by comparing the effects of splenic lymphoid cells from BB/W diabetic (D), diabetes-prone (DP), and diabetes-resistant (DR) rats on the release of 51Cr from damaged islet cells in vitro. D and DP splenic lymphoid cells were cytotoxic to major histocompatibility complex (MHC)-compatible Wistar-Furth (WF) rat islet cells and also to MHC-incompatible Lewis rat islet cells and a rat islet cell line (RIN 5F), whereas WF and Lewis rat spleen cells and a rat pituitary cell line (GH3) were not lysed by lymphoid cells from D or DP rats. The cytotoxic cells were identified as natural killer (NK) cells since NK-sensitive cells (G1-TC and YAC-1 cell lines) were lysed by D and DP spleen cells, YAC-1 cells competed for the lysis of RIN islet cells by D spleen cells, lysis of RIN cells was increased by using D spleen cells from the low density fraction (large lymphocytes/monocytes) of a Percoll density gradient, and incubation of D spleen cells with an antiserum to NK cells (anti-asialo GM1 serum) and complement decreased monoclonal antibody-defined subsets containing NK cells (W3/13+ OX19- and OX8+), and this was accompanied by similar decreases in cytotoxicity to YAC-1, RIN, and WF islet cells. These studies demonstrate that NK cell activity is increased in BB/W diabetic and DP rats, and that islet cells can serve as targets for these NK cells. The findings suggest that NK cells may participate in the islet-directed cellular cytotoxic response leading to beta cell destruction and diabetes.
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PMID:Spontaneous diabetes mellitus in the Bio-Breeding/Worcester rat. Evidence in vitro for natural killer cell lysis of islet cells. 351 4

The BB rat develops a spontaneous type I diabetic syndrome with anti-islet autoimmunity. Sera from diabetic and nondiabetic BB rats (from diabetes-prone litters), nondiabetic BB rats (from low-risk lines), and nondiabetes-prone Sprague-Dawley rats were collected twice a week from age 40 days to 160 days. Sera were tested for: (1) complement-dependent toxicity to 51Cr-labeled islet cells in vitro; (2) immunoglobulin binding to RIN-5 F insulinoma cells; and (3) ability to selectively suppress insulin secretion from normal islets in vitro. All sera from rats that subsequently became diabetic or glucose-intolerant were toxic to islet cells from various rat strains in the presence of complement. They were toxic neither to hepatocytes nor to fibroblasts. The toxic potency was associated with the globulin fraction. It was, in most cases, maximal either before or immediately after the onset of the disease. Sera from the nondiabetes-susceptible BB rats and the rats which, in diabetes-prone litters, died too early to be classified tended toward greater toxicity to islets. Immunoglobulins from diabetic sera bound to RIN-5 F cells more than did the serum globulins from other groups, their maximal binding capacity occurring after the onset of diabetes. Furthermore, BB diabetic sera were capable of selectively inhibiting the insulin secretion from normal rat islets in vitro either in the presence or, in some cases, in the absence of complement. The A- and D-cell functions were not suppressed. The combination of such results suggests the presence of one or more antibodies capable of binding to beta cells, inhibiting their function, and inducing their lysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Sep
PMID:Time course of islet cell antibodies in diabetic and nondiabetic BB rats. 389 99

The selective permeability of alginate microcapsules, containing isolated rat islets of Langerhans or insulin secreting RINm5F cells, was investigated in vitro. An increase in insulin release was observed when microencapsulated islets were stimulated by glucose+theophylline, and when microencapsulated RINm5F cells were stimulated by arginine+theophylline. These findings demonstrate the permeability of the microcapsule membrane to these B-cell secretagogues and to insulin. Immunoisolation of RINm5F cells by microencapsulation was assessed using a 51chromium cytotoxicity test. Significant 51Cr release was observed when nonencapsulated cells were incubated with complement and either the serum of a rabbit immunized with RIN cells or the sera of two patients with recently diagnosed Type 1 (insulin-dependent) diabetes. This effect was not observed with encapsulated cells. Both free and encapsulated cells released 80% of their initial radioactivity when incubated in the presence of HC1. These results clearly demonstrate pancreatic cell immunoisolation by microencapsulation. They also provide a method for the in vitro evaluation of the functional characteristics of microcapsules, in terms of both insulin permeability and immunoprotection.
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PMID:Immunoisolation of pancreatic B cells by microencapsulation. An in vitro study. 393 20

A number of hormones and factors were found to stimulate growth of cultured rat islet tumor cells, the RIN-r cell line. A serum-free supplemented medium from RIN-r cells was formulated. It consisted of a 1:1 mixture of Ham's F12 and DME media with the addition of insulin, transferrin, triiodothyronine, prolactin, growth hormone, and an extract of proteose peptone (medium IM). The growth rate of RIN-r cells in this medium is as great as it is in 10% serum-supplemented medium. Up to 10 populations doublings occurred over a period of 20 days. Insulin is a very effective mitogen for RIN-r cells and has an effect on concentrations as low as 30 ng/ml. In addition, the insulin-like somatomedin, multiplication stimulating activity (MSA), is a growth factor at 50 ng/ml. It was found that RIN-r cells proliferate and continue to produce immunoreactive insulin in a hormonally and nutritionally defined medium. This medium is derived from medium IM, in which insulin is replaced with MSA and proteose peptone is omitted. Variations of this medium may prove useful in studies on the growth and function of the normal islets in long-term primary culture.
Diabetes 1981 Dec
PMID:Hormones and factors that stimulate growth of a rat islet tumor cell line in serum-free medium. 627 46

Calmodulin concentrations were measured in isolated hamster islets or in a cloned rat insulin-secreting cell line RIN-m-5F treated with high glucose. There was no change in the cellular calmodulin content of either islets or RIN-m-5F cells despite increases of insulin concentrations in the media. Treatment of cells with the anti-calmodulin drug W13 inhibited insulin-stimulated glucose release, whereas a small effect on insulin accumulation in the media was observed with W12, the dechlorinated, less active analogue of W13. At the lowest dose tested (30 microM) the effect of W13 on insulin accumulation in the media was completely reversible. To further investigate the possible role of calmodulin in insulin secretion, calmodulin-binding proteins in subcellular fractions of the RIN-m-5F cells were identified using a gel overlay technique. Ca2+-dependent binding of 125I-calmodulin was observed to cytosolic proteins with apparent Mr = 125, 110, 56, 52, and 34 k (kilodalton). This binding was completely displaceable with unlabeled calmodulin, whereas only partial displacement was observed when the homologous Ca2+ binding protein of skeletal muscle, troponin C, was used. Four proteins with Mr similar to the histones bind calmodulin in a Ca2+-independent manner. 125I-calmodulin:calmodulin binding protein interactions were inhibited in a dose-dependent manner by the anti-calmodulin drug, W13. Little effect was observed with the analogue W12.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1983 Dec
PMID:Calmodulin-binding proteins in a cloned rat insulinoma cell line. 631 98

Litters of BB rats with an expected high and low incidence of insulin-dependent diabetes were followed from weaning until the age of about 140 days. Islet cell surface antibodies (ICSA) and lymphocyte antibodies (LA) were determined in a radioligand assay with fixed rat insulinoma (RIN 5F) cells, an insulin-secreting cell line, or spleen lymphocytes. In the low-incidence litter, 2 out of 14 rats had ICSA and LA; one showed insulitis at the end of the study. In the high-incidence litter, 3 out of 7 developed diabetes; all 3 showed ICSA at weaning. The remaining 4 showed insulitis. All 7 diabetes-susceptible rats had ICSA and LA at some time during the study. It is concluded that there is a high incidence of circulating ICSA and LA in the spontaneously diabetic BB rat. The antibodies can often be detected before the onset of diabetes, and may be implicated in the beta-cell destructive process and in the lymphocytopenia characteristic of the syndrome.
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PMID:Humoral immunity in the spontaneously diabetic BB rat. 634 98

Antibodies to normal Wistar rat islet cells are often found in newly diagnosed diabetic BB rats. It was tested if antibodies in BB rats bind to cells from a cloned insulin-producing, rat-insulinoma cell line, RIN 5F, using a protein A-radioligand assay for islet cell surface antibodies. A close correlation was found between the binding of antibodies to islet cells and to RIN 5F cells. Islet cell surface antibodies reactive with RIN 5 F cells were determined in two litters of BB rats, born by diabetic, islet cell surface antibody positive parents. A high incidence (85%) of diabetes was found among 13 offsprings, the mean age of onset being 88 days. At 44 days of age before diabetes was diagnosed, 95% of 20 offsprings were islet cell surface antibody positive. There was no difference in antibody-levels between diabetic and non-diabetic rats. It is concluded that BB rats have circulating antibodies reactive with surface determinants on the RIN-5F insulin-producing cell line. There was a high prevalence of islet cell surface antibodies among young, yet unaffected BB rats.
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PMID:Islet cell surface antibodies in spontaneously diabetic BB rats. 676 51

The present communication describes the generation of twelve lymphocyte hybrid cell lines whose antibodies react with the rat islet cell line RIN, and the initial characterization of the tissue specificity and functional properties of these antibodies. Since antibodies recognizing islet cell differentiation antigens were sought, these permanent hybrid cell lines were developed from cultures whose antibodies, by radioimmunoassay, bound minimally or not at all to rat red blood cells (cell line A3C1 is an exception). Antibodies from five of the cell lines by radioimmunoassay react significantly with cultured rat fibroblasts in addition to their reaction with RIN cells. Antibody F41-5D6 by indirect immunofluorescence reacted with sections of the RISL transplantable islet cell tumor and specifically with islet cells in sections of rat pancreas. Four antibodies (F41-1G3, 5B5, 6C5, and 5A5), by indirect immunofluorescence, reacted with sections of the RISL transplantable islet cell tumor but not with sections of normal pancreas. Seven of the antibodies were cytotoxic to cultured RIN cells and seven antibodies share the useful property of reacting with protein A. This study demonstrates the feasibility of producing monoclonal antibodies to islet cell differentiation antigens and describes several antibodies which should be useful reagents in studies of the physiology and pathophysiology of the islet cell plasma membrane.
Diabetes 1981 Mar
PMID:Production of monoclonal antibodies reacting with rat islet cell membrane antigens. 700 71

An inducible nitric oxide (NO) synthase isoform (iNOS) is specifically induced in the beta-cells of interleukin (IL)-1 beta-exposed rat islets, suggesting a role for NO in the pathogenesis of type I diabetes. The aim of this study was to clone and characterize iNOS cDNA from cytokine-exposed islets. Neither NO production nor iNOS transcription could be detected in rat islets or in rat insulinoma RIN-5AH beta-cells cultured in the absence of cytokines. Addition of IL-1 beta alone or in combination with tumor necrosis factor-alpha induced a concentration- and time-dependent expression of the iNOS gene and associated NO production (measured as nitrite) from both islets and RIN cells. iNOS transcripts were cloned by reverse transcriptase-polymerase chain reaction from the cytokine-exposed rat islets and RIN cells, and DNA sequence analysis revealed a near 100% identity to the recently published iNOS cDNA cloned from cytokine-exposed rat hepatocytes and smooth muscle cells. Recombinant rat islet iNOS was transiently and stably expressed in human kidney 293 fibroblasts, and the high enzymatic activity was inhibited by addition of the L-arginine analogs, N omega-nitro-L-arginine methyl ester and aminoguanidine. Two-dimensional gel electrophoresis revealed the recombinant iNOS as a series of spots with the expected molecular mass of 131 kDa and pI values in the range of 6.8 to 7.0. In conclusion, the IL-1 beta-induced iNOS cloned and expressed from rat islets and RIN cells is encoded by the same transcript as the iNOS induced in other cell types.
Diabetes 1995 Jul
PMID:Cloning and expression of cytokine-inducible nitric oxide synthase cDNA from rat islets of Langerhans. 754 May 73


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