CONTEXT Allotransplantation of islets can successfully treat subjects with type 1 diabetes complicated by severe hypoglycemia and erratic glycemic control. Insulin independence is often lost over time due to several factors, including recurrent autoimmunity. Brittle diabetes (frequent hypoglycemia and labile glycemic control) is common after pancreatectomy. This is ameliorated by auto-islet tra...

The anterior-most ectoderm of ascidian larvae contains the adhesive papillae, or palps, which play an important role in triggering the metamorphosis of swimming tadpoles. In Ciona intestinalis, the palps consist of three conical protrusions within a field of thickened epithelium that form late in embryogenesis, as tailbuds mature into larvae. The palp protrusions express the LIM-homeodomain tra...

The primary cells that participate in islet transplantation are the endocrine cells. However, in the islet microenvironment, the endocrine cells are closely associated with the neurovascular tissues consisting of the Schwann cells and pericytes, which form sheaths/barriers at the islet exterior and interior borders. The two cell types have shown their plasticity in islet injury, but their roles...

MicroRNAs (miRNAs) are non-coding gene products that regulate gene expression through specific binding to target mRNAs. Cell-specific patterns of miRNAs are associated with the acquisition and maintenance of a given phenotype, such as endocrine pancreas (islets). We hypothesized that a subset of miRNAs could be differentially expressed in the islets. Using miRNA microarray technology and quanti...

Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature, islet microenvironment, and β cell mass, we transiently increased VEGF-A production by β cells. VEGF-A...

We have identified a model system for the study of pancreatic islet development and regeneration in transgenic mice bearing the interferon-gamma (IFN-g) gene expressed in the pancreatic islets. Previous studies showed that the locally produced IFN-g causes lymphocyte infiltration and islet cell destruction. Here we demonstrate that new islet cells are formed continuously from duct cells as evid...

B-cells participate in the autoimmune response that precedes the onset of type 1 diabetes, but how these cells contribute to disease progression is unclear. In this study, we analyzed the phenotype and functional characteristics of islet-infiltrating B-cells in the diabetes-prone NOD mouse and in the insulitis-prone but diabetes-resistant (NOD x NOR)F1 mouse. The results indicate that B-cells a...

The effect of maternal diabetes on the foetal endocrine pancreas has been the subject of extensive studies, but a detailed quantitative immunohistochemical investigation is not available. This study was therefore undertaken to investigate the effect of gestational diabetes on the morphology of foetal rat islets. Sections were stained with anti-insulin (B cells) antibodies and were used for morp...

Islet transplantation is a promising cure for diabetes. However, inflammation, allorejection, and recurrent autoimmune damage all may contribute to early graft loss. Pancreatic islets express lower levels of antioxidant genes than most other tissues of the body, and beta-cells in particular are sensitive to oxidative damage. Therefore, damage from oxidative stress may pose a major obstacle to i...

The Edmonton trials have brought about a marked improvement in the short-term rate of success of islet transplantation with rates of insulin-independence of 80% at 1-year being reported by several institutions worldwide. Unfortunately, this rate consistently decreases to 10-15% by 5 years post-transplantation. Several mechanisms have been proposed to explain this apparent 'islet exhaustion', bu...