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Bi Dan - - 2010
We have previously obtained a clonal population of cells from human foreskin that is able to differentiate into mesodermal, ectodermal and endodermal progenies. It is of great interest to know whether these cells could be further differentiated into functional insulin-producing cells. Sixty-one single-cell-derived dermal fibroblast clones were established from human ...
Alexandrescu Sanda - - 2010
Amino-acids stimulate the mammalian target of rapamycin complex(mTORC)1; mTORC1 integrates amino-acid and energy-sensing pathways in beta-cells. Rapamycin inhibits mTORC1. We examined the mTOR pathway and cell cycle data in the exocrine pancreas in diffuse persistent hyperinsulinemic hypoglycemia of infancy (PHHI). Tissues from two diffuse PHHI cases, one pediatric control and ...
Humbert Martine - - 2010
Tyrosine kinases are attractive targets for pancreatic cancer therapy because several are over-expressed, including PDGFRalpha/beta, FAK, Src and Lyn. A critical role of mast cells in the development of pancreatic cancer has also been reported. Masitinib is a tyrosine kinase inhibitor that selectively targets c-Kit, PDGFRalpha/beta, Lyn, and to a ...
Al-Adsani Amani - - 2010
The pancreatic exocrine cell line AR42J-B13 can be reprogrammed to hepatocytes following treatment with dexamethasone. The question arises whether dexamethasone also has the capacity to induce ductal cells as well as hepatocytes. AR42J-B13 cells were treated with and without dexamethasone and analyzed for the expression of pancreatic exocrine, hepatocyte and ...
Prince Victoria E VE Department of Organismal Biology & Anatomy, The University of Chicago 1027 E 57th Street, Chicago, IL 60637 - - 2010
In recent years, there has been significant progress in understanding the detailed mechanisms of pancreas development. These studies have in turn influenced research aimed at producing pancreatic islet cells from stem cells. Here, we review recent progress in both of these areas.
Al-Masri M - - 2010
AIMS/HYPOTHESIS: Recent studies have demonstrated that in adult murine beta cells the forkhead box O1 (FOXO1) transcription factor regulates proliferation and stress resistance. However, the role of FOXO1 during pancreatic development remains largely unknown. The present study aimed to characterise the expression of the FOXO1 transcription factor in the early ...
Chen Ya Wen - - 2010
Mercury is a well-known highly toxic metal. In this study, we characterize and investigate the cytotoxicity and its possible mechanisms of inorganic mercury in pancreatic beta-cells. Mercury chloride (HgCl2) dose-dependently decreased the function of insulin secretion and cell viability in pancreatic beta-cell-derived HIT-T15 cells and isolated mouse pancreatic islets. HgCl2 ...
Wang Sui - - 2010
The basic helix-loop-helix transcription factor Neurog3 (Neurogenin3 or Ngn3) actively drives endodermal progenitor cells towards endocrine islet cell differentiation during embryogenesis. Here, we manipulate Neurog3 expression levels in endocrine progenitor cells without altering its expression pattern using heterozygosity and a hypomorph. Lowered Neurog3 gene dosage in the developing pancreatic epithelium ...
Rovira Meritxell - - 2010
The question of whether dedicated progenitor cells exist in adult vertebrate pancreas remains controversial. Centroacinar cells and terminal duct (CA/TD) cells lie at the junction between peripheral acinar cells and the adjacent ductal epithelium, and are frequently included among cell types proposed as candidate pancreatic progenitors. However these cells have ...
Guoan Xiang - - 2010
BACKGROUND: Myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic member of the B cell lymphoma/leukemia-2 (Bcl-2) family, has been shown to be involved in apoptosis and the cell cycle. Mcl-1 is overexpressed in many malignancies, including pancreatic cancer. The aim of this study was to investigate the effect of siRNA targeted against ...
Ueberberg S - - 2010
Phage display technology is a powerful approach for the generation of peptides and antibodies that target specific organ- or tumor-structures. By applying this approach to rats in vivo or freshly isolated rat islets in vitro, we have recently reported the successful isolation of internalizing single-chain antibodies (SCA-antibodies), which are highly ...
McDonald Erin - - 2009
The transition of pancreatic progenitor cells to mature beta cells is regulated by the interaction of several transcription factors, including members of the sex-determining region on Y box (SOX) family of transcription factors. The SOX proteins are widely involved in cell fate determination and the development of several tissues, including ...
Solar Myriam - - 2009
A longstanding unsettled question is whether pancreatic beta cells originate from exocrine duct cells. We have now used genetic labeling to fate map embryonic and adult pancreatic duct cells. We show that Hnf1beta+ cells of the trunk compartment of the early branching pancreas are precursors of acinar, duct, and endocrine ...
Coad R A RA Stem Cell Institute, University of Minnesota, MTRF, Minneapolis, MN 55455, - - 2009
The biliary system has a close developmental relationship with the pancreas, evidenced by the natural occurrence of small numbers of biliary-derived beta-cells in the biliary system and by the replacement of biliary epithelium with pancreatic tissue in mice lacking the transcription factor Hes1. In normal pancreatic development, Hes1 is known ...
Mancuso Francesca - - 2010
The limited availability of cadaveric human donor pancreata as well as the incomplete success of the Edmonton protocol for human islet allografts fasten search for new sources of insulin the producing cells for substitution cell therapy of insulin-dependent diabetes mellitus (T1DM). Starting from isolated neonatal porcine pancreatic islets (NPIs), we ...
Cai Jun - - 2010
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 ...
Lefebvre Bruno - - 2010
Neurogenin 3 is necessary for endocrine cell development in the embryonic pancreas and has been shown to induce transdifferentiation duct cells from adult pancreas toward a neuro-endocrine phenotype. Here we discovered that the demethylating agent 5'-Azadeoxycytidine (AZA) induced Ngn3 expression and endocrine differentiation from the PANC-1 human ductal cell line. ...
Perides George G Department of Surgery, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02111, USA. - - 2010
The mechanisms by which reflux of bile acids into the pancreas induces pancreatitis are unknown. We reasoned that key events responsible for this phenomenon might be mediated by Gpbar1, a recently identified and widely expressed G-protein-coupled, cell surface bile acid receptor. Acute pancreatitis was induced in wild-type and Gpbar1(-/-) mice ...
Liao Min - - 2010
Huntingtin-associated protein-1 (HAP1) was initially identified as a binding partner of huntingtin, the Huntington's disease protein. Based on its preferred distribution among neurons and endocrine cells, HAP1 has been suggested to play roles in vesicular transportation in neurons and hormonal secretion of endocrine cells. Given that HAP1 is selectively expressed ...
Gidekel Friedlander Sharon Y SY The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, - - 2009
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. To investigate the cellular origin(s) of this cancer, we determined the effect of PDAC-relevant gene mutations in distinct cell types of the adult pancreas. We show that a subpopulation of Pdx1-expressing cells is susceptible to oncogenic K-Ras-induced transformation ...
Gustavsen Carsten R - - 2009
Acomys, also called spiny mice, were once used as a diabetes model. We have recently demonstrated that the closest relatives to the Acomys, members of the family Gerbillinae, lack the transcription factor Pdx-1. Therefore, we sought to determine if members of this family also lack Pdx-1, and describe the pancreatic ...
Rukstalis J Michael - - 2009
The basic helix-loop-helix transcription factor neurogenin-3 (Ngn3, Neurog3) is critical for the development of the endocrine cells of the islets. Either disrupted or forced expression of Ngn3 early in mouse pancreas development abrogates the formation of islets. The successive waves of Ngn3 expression that occur during the primary and secondary ...
Jain R - - 2009
Cell-cell communication within any given tissue is an important aspect of correct organ function. The islets of Langerhans forming the endocrine pancreas are composed of alpha-, beta-, delta-, epsilon- and PP-cells, and interactions between these cells are required for fine-tuning glucose homeostasis of the body. The endocrine cells communicate through ...
Logsdon Craig D CD Department of Cancer Biology and GI Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. - - 2009
The relationship between chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) is unclear. CP is a risk factor for PDAC, CP is found within the vicinity of PDAC, and both share many similar genetic alterations. However, it has been long thought that PDAC arises only from duct cells. However, we ...
Tanaka Hajime - - 2010
Pancreatic ductal adenocarcinoma (PDA) is one of the most debilitating malignancies in humans. A thorough understanding of the cytogenesis of this disease will aid in establishing successful treatments. We have developed an animal model which uses adult Hras(G12V) and Kras(G12V) transgenic rats in which oncogene expression is regulated by the ...
You Hui - - 2009
The adult differentiated insulin-secreting pancreatic islet beta-cell experiences slow growth. This study shows that atrial natriuretic peptide (ANP) stimulates cell proliferation and [(3)H]thymidine incorporation in INS-1E glucose-sensitive rat beta-cell line cells and isolated rat islet DNA. In addition, cGMP, the second messenger of natriuretic peptide receptors (NPR) A and B, ...
Kilimnik German - - 2009
Tracing changes of specific cell populations in health and disease is an important goal of biomedical research. Precisely monitoring pancreatic beta-cell proliferation and islet growth is a challenging area of research. We have developed a method to capture the distribution of beta-cells in the intact pancreas of transgenic mice with ...
Nelson Patrick - - 2009
Type 1 diabetes (T1DM) is a chronic autoimmune disease with a long prodrome, which is characterized by dysfunction and ultimately destruction of pancreatic beta-cells. Because of the limited access to pancreatic tissue and pancreatic lymph nodes during the normoglycemic phase of the disease, little is known about the dynamics involved ...
Park Jong-Kook - - 2009
The contribution of overexpressed microRNA-21 and -221 (miR-21 and miR-221) to the malignant phenotype was determined by inhibiting these miRNAs using antisense oligonucleotides. The effects of antisense to miR-21 and miR-221 on cell proliferation, cell cycle arrest, induction of apoptosis, combinatorial effects with gemcitabine, and effects on target protein levels ...
Granger A - - 2009
Beta-cell regeneration represents a major goal of therapy for diabetes. Unravelling the origin of beta cells during pancreatic regeneration could help restore a functional beta-cell mass in diabetes patients. This scientific question has represented a longstanding interest still intensively investigated today. This review focuses on pioneering observations and subsequent theories ...
Mareninova Olga A OA Veterans Affairs Greater Los Angeles Healthcare System and University of California at Los Angeles, Los Angeles, California 90073, - - 2009
The pathogenic mechanisms underlying acute pancreatitis are not clear. Two key pathologic acinar cell responses of this disease are vacuole accumulation and trypsinogen activation. We show here that both result from defective autophagy, by comparing the autophagic responses in rodent models of acute pancreatitis to physiologic autophagy triggered by fasting. ...
Wescott Melanie P - - 2009
Embryonic development of the pancreas is marked by an early phase of dramatic morphogenesis, in which pluripotent progenitor cells of the developing pancreatic epithelium give rise to the full array of mature exocrine and endocrine cell types. The genetic determinants of acinar and islet cell lineages are somewhat well defined; ...
Desgraz Renaud - - 2009
Pancreatic islet endocrine cells arise during development from precursors expressing neurogenin 3 (Ngn3). As a population, Ngn3(+) cells produce all islet cell types, but the potential of individual Ngn3(+) cells, an issue central to organogenesis in general and to in vitro differentiation towards cell-based therapies, has not been addressed. We ...
Kereszturi Eva - - 2009
Mutations in the activation peptide of human cationic trypsinogen have been found in patients with chronic pancreatitis. Previous biochemical studies demonstrated that mutations p.D19A, p.D22G, and p.K23R strongly stimulate trypsinogen autoactivation. In the present study, we characterized the cell biological effects of these mutants using human embryonic kidney 293T and ...
Guardado-Mendoza R - - 2009
Study of endocrine pathology in animal models is critical to understanding endocrine pathology in humans. We evaluated 434 endocrine-related diagnoses from 4619 baboon necropsies, established the incidence of spontaneous endocrine pathology, and analyzed the clinical and biochemical data associated with the individual cases. The most common diagnoses in descending order, ...
Su Jing J Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, - - 2010
Pancreatic islet encapsulation within semi-permeable materials has been proposed for transplantation therapy of type I diabetes mellitus. Polymer hydrogel networks used for this purpose have been shown to provide protection from islet destruction by immunoreactive cells and antibodies. However, one of the fundamental deficiencies with current encapsulation methods is that ...
Siech Marco - - 2009
Mechanisms leading to acute pancreatitis after a fat-enriched meal combined with excess alcohol are incompletely understood. We have studied the effects of alcohol and fat (VLDL) on pancreatic acinar cell (PAC) function, oxidative stress, and repair mechanisms by pancreatic stellate cells (PSC) leading to fibrogenesis. To do so, PAC (rat) ...
Aviv Vered - - 2009
Over the last few years, evidence has accumulated revealing the unexpected potential of committed mammalian cells to convert to a different phenotype via a process called transdifferentiation or adult cell reprogramming. These findings may have major practical implications because this process may facilitate the generation of functional autologous tissues that ...
Li Juan - - 2009
The differentiation of pancreatic ductal epithelial cells into beta-cells has been considered as an alternative method for increasing the number of islets for transplantation. Critical factors have been introduced into the in vitro differentiation protocol for pancreatic duct cells in order to enhance the production of beta-cells. Islet neogenesis-associated protein ...
Joglekar Mugdha V - - 2009
Epithelial-to-mesenchymal transition is a phenomenon necessary for embryonic development and also seen during certain pathological conditions.  We show here for the first time that reduction in miR-30 family microRNAs, is responsible for mesenchymal transition of primary cultures of human pancreatic epithelial cells.  We found that miR-30 family microRNAs target mesenchymal ...
Braun Matthias - - 2009
Ion channels in the plasma membrane are critical for coupling metabolic signals to hormone release from pancreatic islet cells. The increased availability of human islets for research purposes has recently enabled us to perform a more detailed characterization of ion channels in human β-cells as well as in human δ- ...
Kim Suk Kyoung - - 2010
Islet transplantation is a potential treatment for type 1 diabetes. Currently, islet graft survival is measured using invasive methods to determine blood glucose, insulin, and C-peptide levels, even though these variables have limited value. To trace beta-cell survival and functional status, we constructed an adenovirus/adenoassociate virus hybrid vector (Hyb-DR) carrying ...
Perc Matjaz - - 2009
Calcium ions play an important role in both intra- and intercellular signaling. In pancreatic acinar cells intracellular Ca(2+) regulates exocytotic secretion and fluid secretion. In this paper we study the typical experimental traces of Ca(2+) responses in pancreatic acinar cells obtained in response to the physiological agonist acetylcholine. To determine ...
Kharouta Michael - - 2009
Emerging reports on human islets emphasize distinct differences from the widely accepted prototype of rodent islets, raising questions over their suitability for human studies. Here we aim at elucidating architectural differences and similarities of human versus rodent islets. The cellular composition and architecture of human and rodent islets were compared ...
Husain Sohail S Department of Pediatrics, Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut, - - 2009
This review focuses on studies from the past year that have greatly advanced our understanding of molecular and cellular regulation of pancreatic acinar cell function. Recent advances focus on signals dictating pancreatic development, acinar cell fate, pancreatic growth, and secretion. Regeneration of acinar cells after pancreatitis depends on expression of ...
Eberhard Daniel - - 2009
The endocrine pancreas consists of highly vascularized and innervated endocrine mini-organs--the islets of Langerhans. These contain multiple types of hormone-producing cells, including the insulin-secreting beta-cell. The major task of the fully differentiated beta-cell is the tight regulation of blood glucose levels by secreting insulin into the blood stream. This requires ...
Ren Meng M Departments of Endocrinology and Hepatobiliary Surgery, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou 510120, - - 2009
The feasibility of inducing endocrine pancreatic differentiation of embryonic stem (ES) cells has been well documented. However, whether ES cells possess the potential for exocrine pancreatic differentiation requires further exploration. Here, we investigated whether sodium butyrate and glucocorticoids were conducive to the exocrine pancreatic differentiation of ES cells. E14 mouse ...
Hyder Ayman - - 2010
Sensitivity of pancreatic islets to hypoxia is one of the most important of the obstacles responsible for their failure to survive within the recipients. The aim of this study was to compare the in vitro hypoxia tolerance of neonatal and adult rat islet cells and to study the glucose metabolism ...
Shimizu Hirofumi - - 2009
The present study was designed to establish a novel tissue engineering approach for diabetes mellitus (DM) by fabricating a tissue sheet composed of pancreatic islet cells for in vivo transplantation. Pancreatic islet cell suspensions were obtained from Lewis rats, and plated onto temperature-responsive culture dishes coated with extracellular matrix (ECM) ...
Hehlgans Stephanie - - 2009
BACKGROUND AND PURPOSE: Resistance of pancreatic ductal adenocarcinoma (PDAC) to chemo- and radiotherapy is a major obstacle. The integral membrane protein Caveolin-1 (Cav-1) has been suggested as a potent target in human pancreatic carcinoma cells. MATERIALS AND METHODS: Human pancreatic tumor cells were examined in a three-dimensional (3D) cell culture ...
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