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The HLA-DQ β-chain gene shows a close association with susceptibility or resistance to autoimmune insulin-dependent diabetes mellitus (IDDM) and it has been suggested that the amino acid in position 57 may be of pathogenetic importance. To study the expression of the IDDM associated HLA-DQ β-chain alleles, we immunized rabbits with 12 to 13 amino acid long peptides representing HLA-DQw7 and -DQw8
The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographicall
Basal and yellow fever vaccination-induced 2',5'-oligoadenylate synthetase (2',5'A) activity was determined in blood mononuclear cells (peripheral blood lymphocytes [PBLs]) from insulin-dependent diabetes mellitus (IDDM) and matched control subjects. The live attenuated yellow fever vaccine represented a primary stimulus in all subjects. First, basal 2',5'A activity increased several-fold in respo
Immunocytochemistry combined with morphometry was used to test the hypothesis that insulitis and diabetes are preceded by quantitative changes in the pancreas of diabetes-prone BB (DPBB) rats. Diabetes-resistant BB (DRBB) rats of the w-subline served as controls. In the first part of the study rats aged 15, 30,45, and 60 days were studied. At 60 days preceding both insulitis and onset of diabetes,
The insulin-producing rat islet tumor cell line, RIN-5AH, expresses somatogen binding sites and responds to GH by increased proliferation and insulin production. Affinity cross-linking shows that RIN-5AH cells contain two major GH-binding subunits of Mr 100-130K (110K), which appear to exist as disulfide-linked multimers of Mr 270-350K (300K). In addition, a minor Mr 180K GH-binding protein is ide
The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene wa
Cross-culture contamination of cell lines propagated in continuous culture is a frequent event and particularly difficult to resolve in cells expressing similar phenotypes. We demonstrate that DNA-DNA hybridization to blotted endonuclease-digested cell DNA effectively detects cross-culture contamination to monitor inter-species as well as intra-species cross contamination. An insulin-producing cel
The effect of secretin on glucagon and insulin release and its interaction with glucose has been studied in cultured mouse pancreatic islets by column perifusion. Glucose alone showed the well-known stimulation of insulin release and inhibition of glucagon release. Addition of 10 mM secretin increased glucagon secretion at 3 mM d-glucose by 300% while no change in insulin release could be seen at
Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated the release of insulin at 10mM D-glucose, and their effects were indistinguishable with respect to the dy
Neonatal insulin-dependent diabetes mellitus (IDDM) occurs rarely. A sibship of two HLA-Dw314-positive boys who developed IDDM within the 1st wk of life is described. Although the HLA-D region genotype would be consistent with IDDM associated with islet autoimmunity, islet cell antibodies were negative, but both boys exhibited the presence of a novel autoantibody that reacted specifically with a c
The acute effects of recombinant human interleukin-1 beta (rIL-1) on basal and glucose-stimulated insulin release were investigated in the isolated perfused pancreas. At a concentration of 20 μg/l rIL-1 had no effect on basal insulin release, but increased the total amount of insulin released during first and second phase insulin release in response to 20 mmol/l D-glucose in the rat pancreas (P <
Sera from 40 Swedish children diagnosed as having Type 1 (insulin-dependent) diabetes mellitus during a one year period along with 40 age and geographically matched control subjects were tested for antibodies to a Mr-64000 islet protein by immunoprecipitation of 35S-methionine-labelled rat islet amphiphilic proteins. Of the 40 diabetic patients, 29 (73%) were found to be positive whereas all 40 co
The β-cell function in the perfused pancreas, the total pancreatic insulin content, and the weights of pancreas, kidney, spleen, and total body fat were compared at the age of 30 and 45 days in diabetes-prone and body weight-matched diabetes-resistant male BB rats. These inbred rats had an incidence rate of diabetes at 90 days of age of 80 and 0%, respectively. At day 30, the pancreatic insulin co
The pattern of fall in B-cell function measured as plasma and 24 h urinary C-peptide excretion, as well as levels of islet cell antibodies, insulin antibodies and metabolic parameters, were followed for two years in 39 children aged 1-17 years prospectively from clinical onset of Type 1 (insulin-dependent) diabetes. At onset 32/36 patients had measurable plasma C-peptide (median 0.13 nmol/l). Maxi
Diabetes was induced in BALB/c mice by four injections of a subdiabetogenic dose (40 mg/kg) of streptozotocin in combination with CFA. The treatment increased the plasma glucose from 5.8 ± 0.1 to 22.1 ± 1.3 mmol/liter (n = 9). The diabetic animals had circulating islet cell surface antibodies (75%), and a monoclonal islet cell surface IgM antibody, K56aF3, generated from one of the diabetic BALB/c
