Due to the limited supply of donor pancreas, it is imperative that we identify alternative cell sources that can be used to treat diabetes mellitus (DM). Multipotent adipose tissue-derived stem cells (ADSC) can be abundantly and safely isolated for autologous transplantation and therefore are an ideal candidate. Here, we report the derivation of insulin-producing cells from human or rat ADSC by...

Diabetes mellitus is characterized by disrupted glucose homeostasis due to loss or dysfunction of insulin-producing beta cells. In this work, we characterize pancreatic islet development and function in zebrafish mutant for pdx1, a gene which in humans is linked to genetic forms of diabetes and is associated with increased susceptibility to Type 2 diabetes. Pdx1 mutant zebrafish have the key di...

There has been increasing success with the generation of pancreatic cells from human induced pluripotent stem cells (hiPSCs); however, the molecular mechanisms of the differentiation remain elusive. The purpose of this study was to reveal novel molecular mechanisms for differentiation to PDX1+NKX6.1+ pancreatic endoderm cells, which are pancreatic committed progenitor cells. PDX1+ posterior for...

The origins of liver progenitor cells have been extensively studied, but evidence on the origin of pancreatic precursor cells is currently limited. Pancreatic and duodenal homeobox gene 1 (Pdx1) is one of the earliest known markers for the pancreas. A transgenic mouse line expressing green fluorescent protein (GFP) under the control of the Pdx1 promoter showed that Pdx1/GFP expression was first...

The activity of the insulin gene, Ins, in islet beta cells is thought to arise in part from the synergistic action of the transcription factors Pdx1 and BETA2/NeuroD1. We asked how the binding of these factors to A and E elements many tens or hundreds of base pairs upstream of the start site could influence activity of transcriptional machinery. We therefore tested the hypothesis that the compl...

Hertie Institute of Clinical Brain Research, Department of Medical Genetics and Department of Neuroradiology, University of Tübingen, Tübingen, 4 Institute of Human Genetics, GSF National Research Institute, Neuherberg, Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Department of Neurology, University of Munich, Munich, Germany, Department of Neu...

In order to define the undifferentiated transcriptional factors present in neurogenesis of pancreatic β-islet cells, we studied the effect of Pdx1 in embryonic stem cell derived endocrine lineage. There are undifferentiated transcriptional progenitors Pdx1+/Ptf1a+/Cpa1+ tracking the growth of acini, ducts, α and β-islet cells. The upregulated transcriptional factors Pdx1 and ngn3 specify conseq...

Vitamin B6 is an essential metabolite in all organisms, being required as a cofactor for a wide variety of biochemical reactions. De novo biosynthesis of the vitamin occurs in microorganisms and plants, but animals must obtain it from their diet. Two distinct and mutually exclusive de novo pathways have been identified to date, namely deoxyxylulose 5-phosphate dependent, which is restricted to ...

The development of a variety of enteroendocrine cells of the gut is poorly understood. We tested whether immature intestinal stem cells were switched to multiple enteroendocrine hormone-producing cells by in vitro transfer of a homeobox gene. We transfected the pancreatic-duodenal homeobox 1 gene (Pdx1) into IEC-6 cells, an embryonic intestinal epithelial cell line derived from a normal rat, an...

The pancreas is a mixed exocrine and endocrine gland involved in the control of many homeostatic functions. During embryogenesis, the pancreas arises from dorsal and ventral evaginations of the foregut that will subsequently fuse into a single organ. The characterization of early genes expressed in the developing pancreas is critical to understand its specification and differentiation. Here we ...