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The basic helix-loop-helix transcription factor NeuroD1 regulates cell fate in the nervous system but previously has not been considered to function similarly in the endocrine pancreas due to its reported expression in all islet cell types in the newborn mouse. Because we found that NeuroD1 potently represses somatostatin expression in vitro, its pattern of(More)
Activin A (Act.A), a member of the transforming growth factor beta family of secreted proteins, has been implicated in the regulation of growth and differentiation of various cell types. Betacellulin (BTC), a member of the epidermal growth factor family, converts exocrine AR42J cells to insulin-expressing cells when combined with Act.A. We have used primary(More)
Using immortalized human pancreatic endocrine cell lines, we have shown previously that differentiation into hormone-expressing cells requires cell-cell contact acting in synergy with the homeodomain transcription factor pancreatic duodenal homeobox-1 (PDX-1). Although differentiation is associated with a decrease in cell proliferation, the mechanisms(More)
Cell transplantation therapy for diabetes is limited by an inadequate supply of cells exhibiting glucose-responsive insulin secretion. To generate an unlimited supply of human beta-cells, inducibly transformed pancreatic beta-cell lines have been created by expression of dominant oncogenes. The cell lines grow indefinitely but lose differentiated function.(More)
Prospects for inducing endogenous beta-cell regeneration in the pancreas, one of the most attractive approaches to reverse type 1 and type 2 diabetes, have gained substantially from recent evidence that cells in the adult pancreas exhibit more plasticity than previously recognized. There are two major pathways to beta-cell regeneration, beta-cell(More)
The Wnt pathway effector gene TCF7L2 has been linked to type II diabetes, making it important to study the role of Wnt signaling in diabetes pathogenesis. We examined the expression of multiple Wnt pathway components in pancreases from normal individuals and type II diabetic individuals. Multiple members of the Wnt signaling pathway, including TCF7L2,(More)
Cell lines from the fetal and adult pancreas that were developed by retroviral transfer of the SV40T and ras(val12) oncogenes lose insulin expression but retain extremely low levels of somatostatin and glucagon mRNA. In contrast to expanded populations of primary human islet cells, none of them express the homeodomain transcription factor PDX-1. When that(More)
For more than eighty years, insulin injection has been the only treatment option for all type I and many type II diabetic individuals. Whole pancreas transplantation has been a successful approach for some patients, but is a difficult and complex operation. Recently, it was demonstrated that a glucocorticoid-free immunosuppressive regimen led to remarkably(More)
Achieving normoglycemia is the goal of diabetes therapy. Potentially, there are many ways to achieve this goal, including transplantation of cells exhibiting glucose-responsive insulin secretion. However, to be applicable to the large number of people who might benefit from beta cell replacement, an unlimited supply of beta cells must be found. To address(More)
INTRODUCTION Periodic paralysis associated with hyperthyroidism and hypokalemia is an uncommon disorder reported primarily in Asian males and rarely in children. We report three Hispanic adolescent males who were seen with Graves' disease (GD) and THPP. METHODS The method used was chart review. RESULTS Two of these boys presented with episodes of(More)
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