AIMS Recessive PDX1 (IPF1) mutations are a rare cause of pancreatic agenesis, with three cases reported worldwide. A recent report described two cousins with a homozygous hypomorphic PDX1 mutation causing permanent neonatal diabetes with subclinical exocrine insufficiency. The aim of our study was to investigate the possibility of hypomorphic PDX1 mutations in a large cohort of patients with pe...

Differentiation of early foregut endoderm into pancreatic endocrine and exocrine cells depends on a cascade of gene activation events controlled by various transcription factors. Prior in vitro analysis has suggested that the forkhead/winged helix transcription factor Foxa2 (formerly HNF-3 ) is a major upstream regulator of Pdx1, a homeobox gene essential for pancreatic development. Pdx1 is als...

OBJECTIVE Type I diabetes is an immunologically-mediated devastation of insulin producing cells (IPCs) in the pancreatic islet. Stem cells that produce β-cells are a new promising tool. Adult stem cells such as mesenchymal stem cells (MSCs) are self renewing multi potent cells showing capabilities to differentiate into ectodermal, mesodermal and endodermal tissues. Pancreatic and duodenal homeo...

We have previously shown that mice carrying a null mutation in the homeobox gene ipf1, now renamed to pdx1, selectively lack a pancreas. To elucidate the level at which PDX1 is required during the development of the pancreas, we have in this study analyzed the early stages of pancreas ontogeny in PDX-/- mice. These analyses have revealed that the early inductive events leading to the formation ...

The insulin receptor substrates (IRS proteins) coordinate many signals during insulin and IGF-1 stimulation, including activation of the phosphatidylinositol (PI) 3-kinase and ERK1/2 cascades (1). Although highly homologous and universally expressed, Irs1 and Irs2 display distinct biological function in mice (2). Irs1 strongly promotes somatic growth and mediates insulin action upon carbohydrat...

Pancreatic duodenal homeobox-1 (Pdx1), a transcription factor required for pancreatic development and maintenance of β-cell function, was assessed for a possible role in postnatal β-cell formation from progenitors in the pancreatic ducts by selectively deleting Pdx1 from the ducts. Carbonic anhydrase II (CAII)(Cre);Pdx1(Fl) mice were euglycemic for the first 2 postnatal weeks but showed moderat...

OBJECTIVE The transcription factors (TF) Foxa2 and Pdx1 are key regulators of beta-cell (β-cell) development and function. Mutations of these TFs or their respective cis-regulatory consensus binding sites have been linked to maturity diabetes of the young (MODY), pancreas agenesis, or diabetes susceptibility in human. Although Foxa2 has been shown to directly regulate Pdx1 expression during mou...

In this paper we describe the isolation of a second gene in the newly identified pyridoxine biosynthesis pathway of archaebacteria, some eubacteria, fungi, and plants. Although pyridoxine biosynthesis has been thoroughly examined in Escherichia coli, recent characterization of the Cercospora nicotianae biosynthesis gene PDX1 led to the discovery that most organisms contain a pyridoxine synthesi...

Pancreas duodenum homeobox 1 (PDX1) is essential for pancreas development and β-cell formation; however more studies are needed to clearly illustrate the precise mechanism regarding spatiotemporal regulation of Pdx1 expression during β-cell formation and development. Here, we demonstrate that SIRT1, FOXA2 and a number of proteins form a protein complex on the promoter of the Pdx1 gene. SIRT1 an...

One key step in producing insulin-secreting cells from human embryonic stem (hES) cells is the generation of pancreatic and duodenal homeobox gene 1 (PDX1)-expressing pancreatic progenitor cells. All-trans retinoic acid (RA) has important roles in pancreas development and is widely used to induce pancreatic differentiation of ES cells. When RA was added directly to the activin A-induced hES cel...