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A rat islet tumor subclone, RIN-5AH-T2-B, was cultured with 2 mmol/liter of the proliferation-arresting compound sodium butyrate (NaB). Insulin gene expression and glucose-stimulated insulin release were analyzed and compared with logarithmically proliferating and confluent control cells cultured without NaB. Logarithmically proliferating control cells revealed high insulin gene expression. In the
Inbred lymphopenic, diabetes-prone (DP) and non-lymphopenic, diabetes-resistant (DR) BB rats in a specific pathogen-free (SPF) colony were subjected to a cross-intercross breeding experiment which showed diabetes to segregate as a recessive trait. All DP rats, but none of the DR and F1 rats, developed diabetes. In contrast, about 25% of the F2 rats developed diabetes which made it possible to stud
The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM) in association with marked insulitis in the islets of Langerhans. Since platelet-activating factor (PAF-acether) is involved in allergic and inflammatory reactions, we tested a PAF antagonist, Ginkgolide B (BN 52021) for potential effects on islet inflammation and diabetes. Diabetes prone BB/Wor rats were treated daily fr
Mechanisms underlying the etiology and pathogenesis of insulin-dependent diabetes mellitus (IDDM) are reviewed. Its natural history and associated autoimmune phenomena indicate that IDDM is a systemic disorder resulting in a specific disappearance of pancreatic β cells. Genetic aspects of the disorder include its linkage to HLA class II gene loci, although the manner in which this produces autoimm
Diabetes-prone (DP) BB rats spontaneously develop insulin-dependent diabetes resembling type 1 diabetes mellitus in man. They also exhibit lifelong T cell deficiency. The segregation of both diabetes and lymphopenia was studied in crosses between this inbred line of rats and the related but nondiabetic and nonlymphopenic inbred diabetes-resistant (DR) BB rat line. Diabetes segregated as a single,
Forty-one assays were analysed at the 3rd International Workshop on the standardisation of islet cell antibodies. Analysis of precision demonstrated assays consistently detecting blind duplicates within one doubling dilution and capable of discriminating one doubling dilution differences in islet cell antibody concentration. Some assays, however, reported duplicates discrepantly by more than seven
Site-specific, high affinity polyclonal antisera are effectively and successfully produced by immunizing rabbits with synthetic peptides. The use of these antisera in subsequent immune analysis is often limited because of non-specific binding. We describe a new and simple method to effectively affinity-purify anti-peptide antibodies. To test our system, rabbits were immunized with model peptides r
Long term effects of in vivo treatment with human rIL-1β on diabetogenesis and thyroid disease were determined in the Biobreeding rat. Administration of high dose (10 μg/kg) IL-1β accelerated the onset of insulin-dependent diabetes mellitus compared to saline-injected controls. High dose treatment resulted in goiter development, pronounced LT, reduced serum T4 levels, and overall growth reduction.
Insulin autoantibodies (IAAs) occur in newly diagnosed human insulin-dependent diabetes mellitus (IDDM) patients, but their presence in BB rats is controversial, possibly due to assay differences or variability in the animals studied. To resolve this controversy, IAAs were measured in well-characterized inbred BB rats both in radioligand assays with 125I-labeled rat insulin I or II, respectively,
Restriction fragment length polymorphism using an HLA‐DQ β‐chain genomic probe showed that 63 children with insulin‐dependent (type 1) diabetes mellitus (IDDM) were all (100%) positive for the BamH1 fragments 12 kb and/or 4 kb compared to 98% (62/63) for HLA‐DR3 and/or 4 and 75% (47/63) for HLA‐B8 and/or 15. The 36 (56%) DR3‐positive children were all 4‐kb‐positive; however, a total of 44 (70%) ch
To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal tryps
Antibodies to an M(r) 64,000 protein from human or rat islets have been detected at high frequency in newly diagnosed insulin-dependent diabetic patients. In this study, we show that the antigenic and amphiphilic properties of the rat islet M(r) 64,000 protein resemble that of the human protein. We have analyzed the expression of the M(r) 64,000 protein in populations of pancreatic β and non-β cel
The differential diagnosis between Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes is complicated since no specific markers are available for either disease. In this study, 244 consecutive patients were diagnosed with diabetes mellitus during two years in Malmö (230000 inhabitants), corresponding to an incidence rate of 53·100000-1·year-1. Age, body mass index, HbA1c, C-pept
The effect of immunizing healthy individuals with either tetanus toxoid or yellow fever live attenuated vaccine was examined by measuring interferon (IFN)-dependent oligoadenylate synthetase (2-5A) activity. This enzyme converts ATP into oligonucleotides coupled together in 2'-5' diester bonds. The synthetized products possess among other effects growth inhibiting properties and stimulate a latent
Dithizone, a zinc chelating agent, is known to selectively stain the islets of Langerhans in the pancreas. In the present study, we have used this stain to aid the identification of islets in material obtained by collagenase digestion of human pancreas. Islets were shown to rapidly and reversibly stain red on incubation with dithizone solution. Tissue selected on the basis of dithizone staining wa
Increased levels of circulating immune complexes (IC) have been described in insulin-dependent diabetic (IDD) patients at the time of diagnosis. The aim of the present study was to test whether the spontaneously diabetic BB rat had changes in IC levels at different ages prior to and at onset of IDDM as compared with diabetes resistant BB rats and normal Wistar Furth rats. The IC levels were relate
