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

The primary beta-cell antigen of insulin-dependent diabetes is thought to be a protein with a molecular weight of approximately 64 kD. Hyperthermic incubation and cytokines such as interleukin 1 beta, gamma interferon, and tumour necrosis factor induce synthesis of 64 kD protein by insulinoma cells. By western blot techniques, cross-reactivity was found between this 64 kD protein and monoclonal antibodies directed against Mycobacterium tuberculosis heat-shock protein 65, but not with antibodies directed against a similar epitope of M leprae heat-shock protein 65. Binding of M tuberculosis heat-shock protein 65 antibodies to interleukin-1 beta-treated cells was inhibited by prior addition of serum from insulin-dependent diabetic patients which contained antibodies to 64 kD beta-cell antigen. It is suggested that heat-shock protein 65 may be the 64 kD beta-cell antigen and that autoreactivity to an epitope of heat-shock protein 65 may confer susceptibility to insulin-dependent diabetes mellitus.
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PMID:Heat-shock protein 65 as a beta cell antigen of insulin-dependent diabetes. 197 88

Cultured cells derived from hamster insulinoma (In-111 R1 cells) were placed in 1.4 M dimethyl sulfoxide (Me2SO)-containing RPMI 1640 at 20 degrees C for 20 min. They were frozen to -40 degrees C at a cooling rate of 1.0 or 0.5 degrees C/min, subsequently to -80 degrees C at 3 degrees C/min with a programmable freezer. After being maintained at -80 degrees C, they were rapidly thawed to 37 degrees C. Thawed cells were washed with 0.75 M sucrose for removal of Me2SO. Recovered cells were cultured in 2 ml of RPMI 1640 with 1.3 mM theophylline under a gas phase of 95% air -5% CO2 at 37 degrees C for 2 days. In both cooling rates, frozen-thawed cells discharged more insulin than the thawed in the absence of theophylline. However, this released insulin level was higher in the cells frozen at a cooling rate of 0.5 degrees C/min than that at 1.0 degrees C/min. Moreover, insulin released from frozen-thawed hamster insulinoma cells increased significantly with the addition of 1.3 mM theophylline. Considering that the higher insulin release level at 11.1 mM glucose alone might indicate cellular damage, it is suggested that the cooling rate of 1 degree C/min may be better for cryopreservation of the dispersed cells under the present protocol for the assessment of the function of insulin release.
Diabetes Res Clin Pract 1991 Feb
PMID:Effect of the cooling rate on insulin release from frozen-thawed In-111 cells. 202 80

Amyloid deposition is a common pathological feature in insulinoma and in the islets of the pancreas in type-2 diabetic patients. The present immunohistochemical study revealed that normal B-cells, insulinoma, and amyloid deposits in insulinoma and diabetic pancreatic islets were commonly immunoreactive with antiserum to C-terminal synthetic tetradecapeptide of human islet amyloid polypeptide (IAPP) (24-37). Amyloid fibrils in insulinoma were also positive to IAPP by immunoelectron microscopy. A high level of IAPP was detected in the plasma and tissue of a insulinoma patient by radioimmunoassay suggesting that amyloid deposition in insulinoma is due to overproduction of IAPP. Amyloid deposits immunoreactive to IAPP were also seen in all diabetic pancreatic islets, but in no non-diabetic islets. There was much amyloid deposition in the islets of severe diabetics, whose B-cells demonstrated decreased immunoreactivities for IAPP and insulin. The IAPP content of the pancreas was 649.0 and 847.7 pg/mg wet weight in each of two diabetic patients, and 1034.6 and 1447.7 pg/mg wet weight in two non-diabetic patients. The present study revealed that IAPP is a bioactive peptide secreted from islet B-cells and are amyloidogenic peptide concerned in diabetogenensis and/or the progression of type-2 diabetes mellitus.
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PMID:Islet amyloid polypeptide in insulinoma and in the islets of the pancreas of non-diabetic and diabetic subjects. 203 54

rig, a gene originally isolated from a rat insulinoma cDNA library, codes for a basic 145 amino acid protein [( 1986) Diabetes 35, 1178-1180]. Here we show that the immunoreactivity to a monoclonal antibody against the deduced rig protein and the translation product of rig mRNA comigrated with ribosomal protein S15. The amino acid sequence of ribosomal protein S15 purified from rat liver coincided with that deduced from the nucleotide sequence of rig mRNA, but there were indications that the initiator methionine was removed and the succeeding alanyl residue was monoacetylated. From these results, we conclude that the product of rig is ribosomal protein S15.
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PMID:rig encodes ribosomal protein S15. The primary structure of mammalian ribosomal protein S15. 204 58

Five low doses (40 mg.kg-1.day-1) of streptozotocin were given to CD-1 mice to induce "immune" diabetes with insulitis. T-splenocytes (L3T4+ and Lyt2+) from streptozotocin-treated mice were previously reported to display in vitro an increased binding for Beta cells, preceding the onset of hyperglycaemia and of insulitis. Since heparin inhibits lymphocyte traffic, displays anti-adhesive properties, and attenuates some cell-mediated immune diseases, we have investigated the effects of heparin and N-desulphated heparin: 1) in vivo on low-dose streptozotocin-induced diabetes and insulitis, and 2) in vitro on the increased binding of T-splenocytes from streptozotocin-treated mice to rat insulinoma (RINm5F) cells. Daily subcutaneous low doses (5 micrograms or 10 micrograms) of heparin induced a delay in onset and a reduction of the severity of hyperglycaemia and insulitis (p less than 0.01), and reduced the incidence of diabetes (p less than 0.01). Similar effects were obtained with 5 micrograms daily doses of N-desulphated heparin devoid of anticoagulant activity. In contrast, lower (1 microgram) or higher (200 micrograms) doses of heparin were ineffective. Heparin (10 micrograms) did not modify the "toxic" diabetes induced by a single high dose (200 mg/kg) of streptozotocin. On the other hand, heparin dose-dependently (0.1 microgram/ml to 500.0 micrograms/ml) inhibited the increased binding of splenocytes from streptozotocin-injected mice to RIN cells as compared to splenocytes from control mice. This in vitro anti-adhesive effect was detected when either splenocytes or RIN cells were pretreated with heparin before their co-incubation, and was also obtained with N-desulphated heparin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heparin attenuates low-dose streptozotocin-induced immune diabetes in mice and inhibits the beta-cell binding of T-splenocytes in vitro. 206 56

From 1979 to 1981, questionnaires were sent to 2094 hospitals throughout Japan to investigate the causes of severe hypoglycemic attacks other than the administration of oral hypoglycemic agents or insulin preparations. The survey revealed three main causes for the attacks, of which the first was insulinoma, the second extrapancreatic neoplasms, and the third was insulin autoimmune syndrome (IAS), in descending order. Seven years later, a second survey was carried out, which showed the order of the three disorders as the cause of the hypoglycemic attacks to be the same as in the first survey. In both studies it was suggested that the IAS was frequently induced by thiol compounds.
Diabetes Res Clin Pract
PMID:Insulin autoimmune syndrome is the third leading cause of spontaneous hypoglycemic attacks in Japan. 207 67

Growth hormone (GH) plays a dual role in glucose homeostasis. On the one hand, it exerts an insulin antagonistic effect on the peripheral tissue, on the other hand, it stimulates insulin biosynthesis and beta-cell proliferation. The expression of GH-receptors on the rat insulinoma cell line RIN-5AH-T2-clone B was studied. The binding characteristics with regard to specificity for the native 22 kDa hGH, and the 20 kDa variant were similar to that reported on rat adipocytes. Normal rat islet cells showed a similar affinity for hGH. The RIN cells express GH receptors similar to the cloned liver receptor. It is hypothesized that defects in the receptor expression on the beta-cells may contribute to the susceptibility to develop diabetes.
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PMID:Expression of the growth hormone receptor gene in insulin producing cells. 209 87

A simple and rapid enzyme-linked immunosorbent assay (ELISA) for the detection of islet cell membrane antibodies (ICMA) in the sera of IDDM has been recently established. This new method has been made possible by using affinity purified islet cell membrane antigens from a monoclonal insulin secreting cell line obtained from a transplantable rat insulinoma (RINm5F). One hundred and thirty-three sera of newly diagnosed diabetic patients (duration of symptoms of less than 3 months) were tested, and ICMA positivity was found in 21% of patients. In the same group we found 64% ICA positive subjects, but no correlation has been found between ICA and ICMA. Therefore these two auto-antibodies should be considered as expression of different steps of the autoimmune beta-cell damage. In this light ICMA could represent a very early marker of autoimmune process and it could be useful to recognize, among risk subjects, those who are developing IDDM.
Diabetes Res 1990 Nov
PMID:Serum reactivity against RINm5F purified membrane antigens (ICMA) in newly diagnosed diabetic subjects. 213 3

Splenocytes from low-dose (40 mg.kg-1.day-1) streptozotocin-treated mice were tested for their binding ability to rat insulinoma (RINm-5F) cells in a rosette-forming cell assay, before and during the onset of diabetes. They displayed a higher (p less than 0.0001) RIN-adherence than control splenocytes. Such an enhanced binding of splenocytes from diabetic mice was observed on another B-cell (HIT cell) line, but not on non-B cells (particularly on exocrine pancreatic cells, endocrine cells or natural killer-target cells), suggesting that the increased RIN-binding is B-cell specific. This B-cell specificity was also suggested by the use of increasing splenocytes/RIN ratios showing a saturation of RIN-binding in streptozotocin-treated mice. Depletion of lymphocyte subsets revealed that supernumerary RIN-adherent splenocytes from diabetic mice were mainly T lymphocytes, involving both L3T4+ and Lyt2+ cells. Overall, the increased splenocyte-RIN binding was concomitant with the occurrence of islet destruction, but preceded the onset of hyperglycaemia by five days and even the islet immune infiltration. An increased number of RIN-binding splenocytes was also found in mice treated with 33 mg.kg-1.day-1 of streptozotocin, displaying insulitis but not hyperglycaemia. This phenomenon was not found with splenocytes from mice displaying a "toxic" diabetes induced by a single high dose of streptozotocin. No correlation could thus be found between numbers of RIN-binding splenocytes and blood glucose levels, indicating that this phenomenon was not due to metabolic disturbances. These data describe a new marker of cellular immunity in this animal model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:B cell-adherent splenocytes precede the onset of diabetes in low-dose streptozotocin-treated mice. 213 23

Insulin dependent (type 1) diabetes mellitus is considered to be an autoimmune disease characterized by a specific destruction of the insulin-producing pancreatic beta cells. We have explored the possibilities of raising T cells specific for putative pancreatic beta-cell autoantigens using a xenogeneic system. Mouse T cells were induced against the rat insulinoma cells RIN 5AH-B (RIN) and tested for their specific reactivity. No MHC class II-restricted beta-cell-specific helper T-cell reactivity could be detected within the bulk cultures as measured by proliferation, but a remarkably high cytotoxicity against the RIN cells was observed. The target antigen on the cell surface recognized by the generated cytotoxic T cells was shown to be the rat class I major histocompatibility antigen RT1g, and not a beta-cell or tumour cell-specific antigen associated with RIN cell MHC molecules. Our results demonstrate that it is feasible to evoke a xenogeneic T-cell response against the RIN cells. However, the mouse T cells recognize a dominant epitope present on the expressed rat class I major histocompatibility antigen RT1Ag and not a beta-cell-specific antigen. Hence, we conclude that it appears most unlikely that beta-cell-specific T cells can be raised in the xenogeneic system.
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PMID:Mouse cytolytic T cells reactive with rat islet tumour RIN 5AH-B cells. 213 67


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