Search results for "Islets of Langerhans"
showing 10 items of 46 documents
Mitochondrial reactive oxygen species are obligatory signals for glucose-induced insulin secretion.
2009
OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion. RESEARCH DESIGN AND METHODS—ROS production in response to glucose was investigated in freshly isolated rat islets. ROS effects were studied using a pharmacological approach and calcium imaging. RESULTS—Transient glucose increase …
In-vivo confocal real-time mini-microscopy in animal models of human inflammatory and neoplastic diseases
2007
Background and study aims Although various improvements in tissue imaging modalities have recently been achieved, in-vivo molecular and subsurface imaging in the field of gastroenterology remains a technical challenge. In this study we evaluated a newly developed, handheld, miniaturized confocal laser microscopy probe for real-time in-vivo molecular and subsurface imaging in rodent models of human disease. Materials and methods The minimicroscope uses a 488-nm, single line laser for fluorophore excitation. The optical slice thickness is 7 microm, the lateral resolution 0.7 microm. The range of the z-axis is 0-250 microm below the tissue surface. Imaging was performed using different fluores…
Antibodies to New Beta Cell Antigen ICA12 in Latvian Diabetes Patients
2006
In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria, and assays for the detection of autoantibodies are not available. In consequence, slowly progressive autoimmune diabetes or LADA is likely to be missed. Antibodies to GAD65 and IA-2 are the major immunological markers in autoimmune diabetes. Recently, a new beta cell antigen, called ICA12, has been identified, which has a homology to the SOX family of transcription factors. The aim of the study was to analyze the prevalence of ICA12 antibodies in diabetes mellitus patients and controls from Latvia and to see whether this antigen is important in revealing autoimmunity when antibodies against major antigens are not pr…
Full length cDNA of rat RT1.DMa and RT1.DMb and expression of RT1.DM genes in dendritic and Langerhans cells.
1997
MHC encoded DM heterodimers and classical MHC class II complexes meet in an endosomal/lysosomal compartment where DM heterodimers support peptide loading of MHC class II. Studies on peptide loading of rat class II and on peptide persistence in cells of the dendritic lineage prompted us to establish full length cDNA clones coding for the subunits alpha and beta of rat DM molecules as well as a mAb directed against the luminal moiety of the beta subunit. Here we describe the establishment of the first full length cDNA clones of rat RT1.DMa and RT1.DMb. The mode of expression of RT1.DM at the transcript level in bone marrow culture-derived dendritic cells, in Langerhans cells and in a number o…
Nonparenchymal cells in chronically hyperinsulinemic liver acini of diabetic rats, with special regard to hepatic stellate cells
1998
Abstract Background/Aims: An increase in proliferative activity and other distinct hepatocellular alterations — resembling preneoplastic foci and progressing to hepatocellular tumors — have been shown to develop in liver acini draining the blood from islets of Langerhans, transplanted through the portal vein into the liver of streptozotocin-diabetic rats. Methods: Altered and unaltered liver acini were investigated for possible changes in hepatic stellate cells 4–76 days after islet transplantation. Results: Corresponding to a significant increase in the hepatocellular volume, the volume density of total non-parenchymal cells was significantly reduced in altered compared to unaltered liver …
The basic structural lesion of persistent neonatal hypoglycaemia with hyperinsulinism: deficiency of pancreatic D cells or hyperactivity of B cells?
1984
Pancreatic tissue obtained at subtotal pancreatectomy from 15 infants with persistent hypoglycaemia with hyperinsulinism, and autopsy specimens from 23 age-matched normoglycaemic controls, were studied with morphometric methods after immunocytochemical staining of the four main islet cell types (A, B, D and pancreatic polypeptide cells). In three cases, a focal lesion was detected by gross examination. Macroscopic or microscopic examination did not distinguish the 12 other cases from controls. As found previously, nesidioblastosis was not a specific feature of the pancreas in infantile hypoglycaemia, being observed in age-matched controls as well. In cases with hypoglycaemia the volume dens…
EFFECT OF MICROENCAPSULATION ON OXYGEN DISTRIBUTION IN ISLETS ORGANS
1994
In islet transplantation, limitation of oxygen supply may restrict graft function, particularly when encapsulated tissue is used. Therefore, oxygen tensions (PO2) in isolated islet organs (Brockmann bodies) of Osphronemus gorami were measured. In a thermostatically (37 degrees C) controlled measuring chamber, PO2 values were recorded at subsequent microelectrode positions on a radial track toward the center of the organ. In 2 independent groups, we studied the effect of fluid convection (n = 12) and microencapsulation (n = 12). In both groups, sigmoidal PO2 profiles were found, which permit differentiation in an oxygen-depleted zone surrounding the surface, a steep decline inside the tissue…
Synthesis and evaluation of fluorine-18 labeled glyburide analogs as β-cell imaging agents
2003
Glyburide is a prescribed hypoglycemic drug for the treatment of type 2 diabetic patients. We have synthesized two of its analogs, namely N-[4-[beta-(2-(2'-fluoroethoxy)-5-chlorobenzenecarboxamido)ethyl]benzenesulfonyl]-N'-cyclohexylurea (2-fluoroethoxyglyburide, 8b) and N-[4-[beta-(2-(2'-fluoroethoxy)-5-iodobenzenecarboxamido)ethyl]benzenesulfonyl]-N'-cyclohexylurea (2-fluoroethoxy-5-deschloro-5-iodoglyburide, 8a), and their fluorine-18 labeled analogs as beta-cell imaging agents. Both F-18 labeled compound 8a and compound 8b were synthesized by alkylation of the corresponding multistep synthesized hydroxy precursor 4a and 4b with 2-[(18)F]fluoroethyl tosylate in DMSO at 120 degrees C for …
Compromised central tolerance of ICA69 induces multiple organ autoimmunity
2014
For reasons not fully understood, patients with an organ-specific autoimmune disease have increased risks of developing autoimmune responses against other organs/tissues. We identified ICA69, a known β-cell autoantigen in Type 1 diabetes, as a potential common target in multi-organ autoimmunity. NOD mice immunized with ICA69 polypeptides exhibited exacerbated inflammation not only in the islets, but also in the salivary glands. To further investigate ICA69 autoimmunity, two genetically modified mouse lines were generated to modulate thymic ICA69 expression: the heterozygous ICA69(del/wt) line and the thymic medullary epithelial cell-specific deletion Aire-ΔICA69 line. Suboptimal central neg…
In Vitro Cultured Islet‐Derived Progenitor Cells of Human Origin Express Human Albumin in Severe Combined Immunodeficiency Mouse Liver In Vivo
2004
Studies in rodents suggest the presence of a hepatopancreatic stem cell in adult pancreas that may give rise to liver cells in vivo. The aim of the present study was to determine the ability of human islet-derived cells to adopt a hepatic phenotype in vivo. Cultured human islet-derived progenitor cells that did not express albumin in vitro were stained with the red fluorescent dye PKH26 and injected into the liver of severe combined immunodeficiency mice. After 3 or 12 weeks, red fluorescent cells were detected in 11 of 15 livers and were mostly single cells that were well integrated into the liver tissue. Human albumin was found in 8 of 11 animals by immunohistochemistry, and human albumin…