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)

RINmRH cells are a cloned cell line derived from a transplantable rat insulinoma. These cells display only some of the differentiated structure/function features of native pancreatic B-cells. In particular, they do not efficiently or reproducibly express islet B-cell surface antigens, which would otherwise render them useful for screening for the presence of anti-islet cell surface antibodies in the serum of suspected diabetic patients or their relatives. This study examines whether sodium butyrate can enhance expression of B-cell differentiation antigens on RIN cells. RIN cells were exposed to 1,2 or 4 mM butyrate for nine days, and cell growth followed. At 1 mM, butyrate inhibited cell growth by 90%. At the higher concentrations, there was a net loss in the number of cells per culture dish. Exposing the cells to 1 mM or 2 mM butyrate for two days, resulted in a 50% increase in cellular insulin content at the expense of a partial (1 mM) or complete (2 mM) loss of stimulated insulin release in response to glyceraldehyde or serine. A concentration of 1 mM butyrate was therefore used for subsequent studies. The binding to RIN cells of a panel of monoclonal antibodies (mAb's) known to bind native islet cells (R2D6, A2B5, A1D2, 3G5) as well as of serum from a diabetic patient known to carry anti-islet cell antibodies, was screened by cytofluorography or by a radio-binding assay. The relative binding affinity of the mAb's was 3G5 greater than A1D2 greater than A2B5 greater than R2D6. Only 2-3% of the cells were bound by the diabetic patient serum.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1989 Oct
PMID:Modulation by sodium butyrate of the differentiated status of a clonal pancreatic B-cell line (RIN). 269 45

A 64-yr-old man with benign monoclonal gammopathy developed recurrent episodes of severe hypoglycemia but lacked evidence of insulinoma or exogenous insulin administration. The patient's plasma was found to contain anti-insulin antibodies and large amounts of extractable insulin (1110 microU/ml), which was identified as human insulin by high-performance liquid chromatography (HPLC). The anti-insulin antibodies consisted solely of IgG and lambda-light chains. Scatchard analysis of these antibodies revealed an almost straight-line relationship, with markedly low affinity and high capacity. An immune complex made of 125I-labeled insulin and the patient's antibodies emerged in a molecular-sieve HPLC as almost a single peak, suggesting a homogeneous antibody population. In addition, the patient's M protein was separately shown to be the IgG and lambda-light-chain type. We suggest that the insulin autoantibodies responsible for the spontaneous hypoglycemia in this patient are monoclonal and of M protein origin.
Diabetes Care 1989 Feb
PMID:Insulin autoimmune syndrome associated with benign monoclonal gammopathy. Evidence for monoclonal insulin autoantibodies. 270 96

Specific gastric inhibitory polypeptide (GIP) receptors were characterized in human benign insulinoma plasma membranes employing [mono-[125I]iodo-Tyr10]-GIP (125I-GIP) as the radioligand. GIP 1-42 inhibited 125I-GIP binding with an IC50 value of 10(-9) M. Scatchard analysis showed two classes of binding sites: a high-affinity site (Kd = 2.23 x 10(-10) M; Bmax = 24 fmol/mg protein) and a low-affinity site (Kd = 8.39 x 10(-9) M; Bmax = 118 fmol/mg protein). A synthetic replicate of human GIP 1-31 inhibited 125I-GIP binding with an IC50 value of 10(-8) M. The GIP binding sites of human insulinoma were coupled to adenylate cyclase stimulation. GIP 1-31 regulated the adenylate cyclase activity to the same extent as GIP 1-42. The concentrations of GIP required for maximal activity ranged from 10(-9) to 10(-8) M for either GIP 1-42 or GIP 1-31. The existence of functional GIP receptors in human insulinoma substantiates our recent reports demonstrating the presence of GIP binding sites in transplantable hamster insulinoma and indicates that GIP could exert a direct control of the beta-cell function in humans through a purely endocrine pathway.
Diabetes 1987 Nov
PMID:Evidence of functional gastric inhibitory polypeptide (GIP) receptors in human insulinoma. Binding of synthetic human GIP 1-31 and activation of adenylate cyclase. 282 18

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

The In-R1-G9 cell line is one of the clones derived from the In-111-R1 hamster insulinoma cell line and produces glucagon. The secretory responses of In-R1-G9 cells were further examined to characterize the nature of the cells. Vincristine had no effect on glucagon secretion and colchicine enhanced glucagon secretion slightly after a short incubation. Two calmodulin inhibitors, trifluoperazine and chlorpromazine, did not affect glucagon secretion. Monensin at 10(-8) M suppressed glucagon secretion by 50%. Secretion of glucagon was calcium-dependent. The addition of A23187 to the incubation medium resulted in a 180% increase over control for 1 h and calcium deprivation from the medium suppressed glucagon secretion markedly. Theophylline, a phosphodiesterase inhibitor, caused a 230% increase in glucagon secretion. An experiment using cycloheximide suggested that newly synthesized glucagon appears in the medium at 30 min. This cell line should be useful for various experiments in many fields of research.
Diabetes Res Clin Pract 1988 Feb 19
PMID:Characterization of secretory responses of a glucagon-producing In-R1-G9 cell line. 283 60

Glucose metabolism was investigated in two established clonal insulinoma cell lines (RINm5F and HIT) and in a newly developed line of mouse insulinoma cells (IgSV195). The hexokinase capacity in the homogenates of RINm5F cells was 22.1 +/- 3.23 U/g protein, but glucokinase was barely detectable (0.06 +/- 0.013 U/g protein). In contrast, both HIT and IgSV195 cells contained glucokinase (1.5 +/- 0.17 and 1.0 +/- 0.16 U/g protein, respectively) in addition to hexokinase activity. Glucose usage by the intact cells qualitatively reflected the glucose phosphorylation found in the cell-free extracts. RINm5F cells exhibited a high glucose usage rate with one high-affinity component, whereas both HIT and IgSV195 cells showed two components with different glucose affinities. HIT and IgSV195 cells may be useful for a model of pancreatic beta-cell glycolysis.
Diabetes 1988 May
PMID:Control of glucose phosphorylation and glucose usage in clonal insulinoma cells. 283 51

Viruses are implicated in the pathogenesis of beta-cell destruction in type I (insulin-dependent) diabetes. The aim of our study was to investigate whether reovirus 1 or reovirus 3, which are known to infect beta-cells and induce autoimmunity in susceptible mice, could alter the expression of the major histocompatibility complex (MHC) proteins by human beta-cells and rat insulinoma RINm5F cells. Forty-eight hours after infection of either human beta-cells or RINm5F cells with reovirus 1 or reovirus 3, cytopathic effects were noted. By flow-cytofluorometric analysis, infected RINm5F cells exhibited a seven- to eightfold increase in the surface expression of class I MHC proteins. Upregulation of class I MHC proteins on reovirus 3-infected RINm5F cells was inhibited by 80% after preexposure of the virus to reovirus 3 antiserum. When analyzed by double-indirect immunofluorescence microscopy, human beta-cells infected with reoviruses 1 or 3 also exhibited markedly increased levels of class I MHC proteins. Reovirus infection of human beta-cells or RINm5F cells was not accompanied by the induction of class II MHC proteins. These findings suggest that 1) in addition to direct cytopathic effects, reovirus infection may contribute to beta-cell destruction by increasing expression of class I MHC proteins and therefore reactivity with cytotoxic T-lymphocytes; and 2) some viruses may increase MHC protein expression independent of and before the action of cytokines (e.g., interferon-gamma and tumor necrosis factor) released by immunoinflammatory cells.
Diabetes 1988 Mar
PMID:Reovirus infection enhances expression of class I MHC proteins on human beta-cell and rat RINm5F cell. 283 51

The ability of recombinant interferon-gamma (rIFN-gamma) to induce major histocompatibility complex (MHC) antigen expression in the rat insulinoma cell line RINm5F was investigated. The cells were stained with monoclonal antibodies specific for rat class I and class II MHC antigens. RINm5F cells endogenously expressed class I antigens; this was enhanced by rIFN-gamma. Class II antigens could not be detected on RINm5F cells, but both I-A and I-E were induced by rIFN-gamma.
Diabetes 1988 Feb
PMID:Interferon-gamma induces class II MHC antigens on RINm5F cells. 283 86

An hyperglycaemic metabolic state disappeared and spontaneous hypoglycaemia occurred in a 58-year-old woman with non-insulin-dependent obese type II diabetes. Abnormal absence of the hunger response with provoked hypoglycaemia, increased serum insulin concentrations and reduced blood glucose/insulin ratio led to the diagnosis of pathological hyperinsulinism, which was found to be due to an insulinoma of the tail of the pancreas. After its excision the patient's carbohydrate metabolism returned to a mild type II diabetic state and there were no further hypoglycaemic attacks.
 ...
PMID:[Hypoglycemia caused by insulinoma in diabetes mellitus]. 284 54

The authors wanted to test the long-term effectiveness of immunoisolation in the NOD mouse, an adequate model of Type I diabetes. Recipients were diabetic female NOD mice with sustained plasma glucose levels above 400 mg/100 ml. They were grafted intraperitoneally with permselective hollow fibers seeded with human insulinoma (n = 6), rodent insulinoma (n = 6), or human islets (n = 6). Controls were 15 nontreated diabetic females and 10 nondiabetic male NOD mice implanted with nonseeded macrocapsules. Electron microscopy (rectangular crystalline nucleoids characteristic of B-cells), in vitro release of insulin (during abrupt changes in glucose concentration from 40 to 400 mg/dl and return, M +/- SD insulin levels were 122 +/- 5 uu/ml and 315 +/- 17 at low and high glucose), evidence of binding hormone receptors (VIP and GIP, the binding sites being coupled with adenylyl cyclase stimulation) were used to assess the quality of the transplant. Survival was always prolonged in grafted animals. Taking complete and long-term (less than 3 months) correction of hyperglycemia as the criterion, the success rate was about 50% as observed in streptozotocin rats. Splenocytes isolated from cured and not cured recipients and injected into irradiated nondiabetic male NOD mice were always able to transfer the disease. Our bioartificial pancreas is efficient in preventing the recurrence of the disease in autoimmune diabetes.
 ...
PMID:Bioartificial pancreas in autoimmune nonobese diabetic mice. 284 60


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