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Specific pancreatic β-cell surface antigens recognized by a xenogenic antiserum
An antiserum (R4) from a rabbit immunized with suspensions of C57BL/6J ob/ob mouse islet cells contains antibodies which in a 125I-protein A radioligand assay can be demonstrated to bind to single cell suspensions of normal Naval Medical Research Institute (NMRI) mouse islet cells. The binding of 125I-protein A to islet cells was about four times that of normal rabbit serum (NRS) after incubation
Metabolic and underlying causes of diabetes mellitus
It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune pheno
Effects of islet cell surface antibodies and complement on the release of insulin and chromium from perifused β cells
The dynamics of insulin and chromium release from prelabelled rat pancreatic islet cells were studied by perifusion of cells supported in a column of Bio-Gel P-2 polyacrylamide beads. The column-perifused β cells released insulin in a biphasic pattern in response to 30 mmol/l D-glucose and in a monophasic pattern to 20 mmol/l L-arginine. Rat islet cells, first exposed to a rabbit anti-rat islet c
The low dose streptozotocin murine model of Type 1 (insulin-dependent) diabetes mellitus : Studies in vivo and in vitro of the modulating effect of sex hormones
The influence of sex on pancreatic islet B cell susceptibility to streptozotocin was studied in mice given multiple low doses of streptozotocin. Male C3 D2 F1 mice developed a steadily increasing blood glucose level after a lag period of about 3 weeks, in contrast to females who were resistant. Spleen cells from streptozotocin treated female animals produced hyperglycaemia in total body irradiated
New approaches to therapy and diagnosis of diabetes
Not only has recombinant DNA added another source of insulin for treatment, but also, and perhaps more important, it has allowed the development of new techniques for studying the structure and function of the B cell at the gene level. We can only hope that this information will bring us closer to the understanding of the disease, so the diabetic patient may benefit from other measures of treatmen
Absence of H-2 genetic influence on streptozotocin-induced diabetes in mice
Five daily injections of streptozotocin (40 mg/kg) produced a delayed but progressively increasing level of hyperglycaemia in long term studies with male Naval Medical Research Institute mice and C3D2F1 (DBA 2 J male × C3H/ Tif female) F1 hybrid mice. The development of hyperglycaemia was paralleled by decreased amounts of pancreatic immunoreactive insulin as well as degranulation and necrosis of
Islet Transplantation in Mice Differing in the I and S Subregions of the H‐2 Complex : Effects of Presensitization with Skin Allografts
Pancreatic islets from A.TH mice were transplanted into the spleen or streptozotocin (SZ)‐diabetic A.TL mice. The two strains of mice are congenic inbred strains, differing only in the I and S subregions of the H‐2 complex. The allogeneic islet grafts decreased blood glucose temporarily, but the islets were rejected after 21 ± 7 days (mean ± SD). The effect of skin presensitization was tested by g
Autoantibodies in newly diagnosed diabetic children immunoprecipitate human pancreatic islet cell proteins
Insulin-dependent diabetic (IDD) patients have a high prevalence of circulating autoantibodies against islet of Langerhans cells at the time of diagnosis1-4. Inflammatory cells within the islets5, leukocyte migration inhibition in response to pancreatic antigens6 and an association with certain HLA-D/DR histocompatibility antigens 7,8, have also been observed. It seems that the autoantibodies may
Islet cell antibodies - Theoretical and practical implications
An in vitro, sex dependents, and direct cytotoxic effect of streptozotocin on pancreatic islet cells.
A prospective analysis of antibodies reacting with pancreatic islet cells in insulin-dependent diabetic children
Islet cell cytoplasmic and cell surface antibodies along with other autogenic tissue antibodies were determined prospectively from the day of diagnosis of insulin-dependent diabetes in a group of children and adolescents. Prior to the initiation of insulin therapy 30 out of 33 were antibody-positive, 67% having islet cytoplasmic antibodies and 67% islet cell surface antibodies. Among 74 age- and s
Light scattering analysis of rat and mouse islet cells in the fluorescence-activated cell sorter
Islet transplantation in mice differing in the I and S subregions of the H-2 complex
Diabetic A.TL and A.TH mice, congenic inbred strains differing only in the I and S (non-K, non-D) regions of the major histocompatibility (H-2) complex, received intrasplenic allogeneic and isogeneic pancreatic islet transplants. The isografts were uniformly accepted, while approximately 60% of the recipients receiving allografts rejected the islets, most within 4 weeks of transplantation. With ei
Effect of diabetes on islet area and β-cell function
Block in insulin release from column-perifused pancreatic β-cells induced by islet cell surface antibodies and complement
Dispersed rat pancreatic islet cells were mixed into a short column of Bio-Gel P-2 polyacrylamide beads and perifused with an antiserum containing islet cell surface antibodies. The release of radioactive chromium from prelabeled cells, as a measure of cell membrane permeability, was not affected by cell surface antibodies alone, but increased dramatically in the presence of complement. While ther
A major loss in islet mass and b-cell function precedes hyperglycemia in mice given multiple low doses of streptozotocin
Streptozotocin (SZ) given in five low doses causes diabetes and an associated lymphocytic infiltration of the pancreatic islets. Using C57BL/KsJ-mice, we demonstrate a reduction in islet number (-38%) and volume (-64%) within 1 day following the last injection of SZ. A substantial fall of insulin secretory capacity (-84%) in the in vitro perfused pancreas matches the reduction in islet cell volume
Autoimmunity in insulin-dependent diabetes mellitus
Genetic susceptibility, environmental factors and immune mechanisms are implicated in the pathogenesis and etiology of insulindependent diabetes mellitus. The onset of the disease is associated with a major loss of beta cells, and inflammatory cells may be seen in and around the islets of Langerhans. Insulin-dependent diabetes is often associated with autoimmune endocrinopathies. Antipancreatic ce
Ontogenetic patterns of thyrotropin-releasing hormone-like material in rat hypothalamus, pancreas, and retina : Selective effect of light deprivation
Recent observations have shown the presence of thyrotropin-releasing hormone-like material (TRH-LM) in rat pancreatic islets and in retina. Its immunological and biological properties are identical to those of synthetic thyrotropin-releasing hormone (thyroliberin). This communication deals with the ontogenesis of TRH-LM in rat pancreas and retina as compared to that of rat hypothalamus. Effects of
Direct streptozotocin toxicity on dispersed mouse islet cells determined by [ 51]CR-release
Dispersed islet cells were prepared from collagenase-isolated lean mouse pancreatic islets by Dispase-II and subsequent mechanical treatment in calcium depleted media. An average yield of 600 cells per islet was obtained, 84% of the cells being β-cells. Cells were incubated with radioactive chromium as a marker of cell viability. Optimal labelling of 1-2 cpm per cell was obtained by incubating 10
