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Xu Zhihong - - 2010
Pancreatic stellate cells (PSCs) produce the stromal reaction in pancreatic cancer (PC), and their interaction with cancer cells facilitates cancer progression. This study investigated the role of human PSCs (hPSCs) in the metastatic process and tumor angiogenesis using both in vivo (orthotopic model) and in vitro (cultured PSC and PC ...
Kelly Catriona - - 2010
Pseudoislet studies have concentrated on single beta-cell lines or a combination of insulin and glucagon-secreting cells, overlooking the potential role of somatostatin in insulin release. This study sought to evaluate a heterotypic pseudoislet model containing insulin- (MIN6), glucagon- (αTC1.9) and somatostatin (TGP52)-secreting cells of mouse origin and to compare these ...
Volchuk A - - 2010
Eukaryotic cells respond to stress in the endoplasmic reticulum (ER) resulting from insufficient protein folding capacity or altered ER homeostasis by activating the unfolded protein response (UPR). In mammalian cells the UPR is mediated by at least three ER-localized sensors/transducers, and the cellular response and susceptibility to ER stress is ...
Mazilu Jaime K - - 2010
The adrenal cortex and pancreatic islets have endocrine functions, producing steroid-based hormones and insulin, respectively. Cells of the adrenal cortex originate in the mesoderm while the cells of pancreatic islets originate in the endoderm. The zebrafish is a powerful model for understanding organ development due to its ease of genetic ...
Lee Hyeung Sik - - 2010
The regional distribution and frequency of the pancreatic endocrine cells in the ddN mouse were studied using specific antisera against insulin, glucagon, somatostatin and human pancreatic polypeptide (hPP). In the pancreatic islets, most of insulin-immunoreactive (IR) cells were located in the central region, and glucagon-, somatostatin and hPP-IR cells were ...
Liu Shi-He SH Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, - - 2011
Pancreatic-duodenal homeobox 1 (PDX-1) is a transcription factor that regulates embryologic pancreas development and insulin expression in the adult islet; however, it is overexpressed in many types of cancer, including pancreatic cancer. The purpose of this study was to investigate the role of PDX-1 in tumorigenesis in human cells. In ...
Kalousova Anna A Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, - - 2010
All metazoans use insulin to control energy metabolism, but they secrete it from different cells: neurons in the central nervous system in invertebrates and endocrine cells in the gut or pancreas in vertebrates. Despite their origins in different germ layers, all of these insulin-producing cells share common functional features and ...
Hegyi Péter - - 2011
There is an unacceptably high mortality in acute pancreatitis, which is due to the lack of specific treatments for the disease. A major reason stated to account for the inability to develop effective treatments is that there are multiple pathobiologic pathways activated in the acinar cell mediating pancreatitis making it ...
Cui Ju - - 2011
Suppression of Kinesin-1 by antisense oligonucleotides, or overexpression of dominant-negative acting kinesin heavy chain, has been reported to affect the sustained phase of glucose-stimulated insulin secretion in β-cells in vitro. In this study, we examined the in vivo physiological role of Kinesin-1 in β-cell development and function. A Cre-LoxP strategy ...
Hong Seung-Mo SM Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21231, - - 2011
Telomeres protect against chromosomal breakage, fusion, and interchromosome bridges during cell division. Shortened telomeres have been observed in the lowest grade of pancreatic intraepithelial neoplasia (PanIN). Genetically engineered mouse models of pancreatic neoplasia develop acinar-to-ductal metaplasia prior to the development of PanIN, suggesting that acinar-to-ductal metaplasias can be an early ...
Ramachandran P Veeraraghavan - - 2010
A selected series of racemic α-methylene-γ-butyrolactones (AMGBL) were synthesized via allylboration and screened against three human pancreatic cancer cell lines (Panc-1, MIA PaCa-2, and BxPC-3). This systematic study established a discernible relationship between the substitution pattern of AMGBL and their anti-proliferative activity. β,γ-diaryl-AMGBLs, particularly those with a trans-relationship exhibited higher ...
Hu Jia - - 2010
Human islet amyloid polypeptide (hIAPP) deposit is the hallmark of type 2 diabetes pathology. Here, we report that apo-cyclen, attached to a specific hIAPP recognition motif (NYGAIL), captured copper ions and became proteolytically active. This cyclen-NYGAIL-copper complex was able to interfere with hIAPP aggregation and cleave hIAPP. These activities rescued ...
Mannering S I - - 2010
Type 1 diabetes (T1D) is an autoimmune disease caused by the T cell-mediated destruction of the pancreatic insulin-producing beta cells. Currently there are no widely accepted and standardized assays available to analyse the function of autoreactive T cells involved in T1D. The development of such an assay would greatly aid ...
Mei Ying Y Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, - - 2010
We developed a high throughput micro-arrayed polymer system for the study of polymer surfaces for islet cell culture. A micro-arrayed library with 496 different polymers was synthesized and used to examine attachment and insulin expression of islet cells. While most polymers were not supportive, several related polymers were identified as ...
Daval Marie M Larry Hillblom Islet Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, - - 2010
Type 2 diabetes involves aberrant misfolding of human islet amyloid polypeptide (h-IAPP) and resultant pancreatic amyloid deposits. Curcumin, a biphenolic small molecule, has offered potential benefits in other protein misfolding diseases, such as Alzheimer's disease. Our aim was to investigate whether curcumin alters h-IAPP misfolding and protects from cellular toxicity ...
Williams John A JA Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109-5622, USA. - - 2010
This review identifies and puts into context the recent articles which have advanced understanding of the functions of pancreatic acinar cells and the mechanisms by which these functions are regulated. Receptors present on acinar cells, particularly those for cholecystokinin and secretin, have been better characterized as to the molecular nature ...
Eberhard Daniel - - 2010
The clonal structure of the pancreas was analysed in neonatal and adult mouse chimeras in which one partner displayed cell patches expressing green fluorescent protein (eGFP). Coherent growth during pancreatic histogenesis was suggested by the presence of large eGFP-labelled acinar clusters rather than a scattered distribution of individual labelled acinar ...
Banerjee Ipsita - - 2011
Promise of cellular therapy for type 1 diabetes has inspired the search for transplantable cell sources, and embryonic stem cells (ESCs) have emerged as strong candidates. We have developed a directed differentiation protocol to obtain insulin-producing cells from ESCs. The ESCs are first induced towards a homogeneous monolayer of definitive ...
Lausier James - - 2010
The physiological mechanisms that preserve pancreatic β-cell mass (BCM) are not fully understood. Although the regulation of islet function by the autonomic nervous system (ANS) is well established, its potential roles in BCM homeostasis and compensatory growth have not been adequately explored. The parasympathetic vagal branch of the ANS serves ...
Magombedze Gesham - - 2010
Type 1 diabetes is a disease characterized by progressive loss of β cell function due to an autoimmune reaction affecting the islets of Langerhans. Two types of T cells are involved in diabetes: turncoat auto-reactive T cells, or T cells gone bad, that kill the insulin-producing cells, and regulatory T ...
Pisania Anna A Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. - - 2010
Despite improvements in outcomes for human islet transplantation, characterization of islet preparations remains poorly defined. This study used both light microscopy (LM) and electron microscopy (EM) to characterize 33 islet preparations used for clinical transplants. EM allowed an accurate identification and quantification of cell types with measured cell number fractions ...
Fomina-Yadlin Dina D Howard Hughes Medical Institute, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA - - 2010
High-content screening for small-molecule inducers of insulin expression identified the compound BRD7389, which caused alpha-cells to adopt several morphological and gene expression features of a beta-cell state. Assay-performance profile analysis suggests kinase inhibition as a mechanism of action, and we show that biochemical and cellular inhibition of the RSK kinase ...
Lavoie Elise G - - 2010
Extracellular nucleotides and adenosine regulate endocrine pancreatic functions such as insulin secretion by Langerhans islet β-cells via the activation of specific P2 and P1 receptors. Membrane-bound ectonucleotidases regulate the local concentration of these ligands and consequently control the activation of their receptors. The objective of this study was to identify ...
Chen Huiping - - 2010
Accumulating data suggest the existence of a link between hypoxia and maintenance of the undifferentiated cell state, but little is known about the cellular signaling mechanisms underlying this process. Recent reports reveal a direct link between components of the hypoxia signaling pathway and Notch pathway in maintaining precursor cells in ...
Wang Gen-Sheng - - 2010
Type 1 diabetes is inhibited in diabetes-prone BioBreeding (BBdp) rats fed a low-antigen hydrolyzed casein (HC) diet. In cereal-fed BBdp rats, islet expansion is defective accompanied by a futile upregulation of islet neogenesis without increased islet mass, due to a subtle blockage in islet cell cycle. We hypothesized that islet ...
Zhang Xinxia - - 2010
Diabetes has merged as a significant health problem. This study aims to examine the effect of concurrently using rosiglitazone (RSG) on inhibiting glucosamine (GlcN)-induced islet beta cell apoptosis and dysfunction. Using an islet beta cell line, HIT-T15 cells, as a study platform, the inhibitory effect of RSG on GlcN-induced pathophysiological ...
Ryan Gemma A GA Medical Research Council Center for Immune Regulation, University of Birmingham Medical School, Birmingham, United - - 2010
The entry of autoreactive T cells into the pancreas is a critical checkpoint in the development of autoimmune diabetes. In this study, we identify a role for B1 cells in this process using the DO11 x RIP-mOVA mouse model. In transgenic mice with islet-specific T cells, but no B cells, ...
Li Wan-Chun - - 2010
The adult pancreas has considerable capacity to regenerate in response to injury. We hypothesized that after partial pancreatectomy (Px) in adult rats, pancreatic-duct cells serve as a source of regeneration by undergoing a reproducible dedifferentiation and redifferentiation. We support this hypothesis by the detection of an early loss of the ...
Perán Macarena - - 2011
Diabetes type I is an autoimmune disease characterized by the destruction of pancreatic insulin-producing (beta-) cells and resulting in external insulin dependence for life. Islet transplantation represents a potential treatment for diabetes but there is currently a shortage of suitable organs donors. To augment the supply of donors, different strategies ...
Hall K K - - 2011
Functionalized alginate and poly(ethylene glycol) (PEG) polymers were used to generate covalently linked alginate-PEG (XAlgPEG) microbeads of high stability. The cell-compatible Staudinger ligation scheme was used to cross-link phosphine-terminated PEG chemoselectively to azide-functionalized alginate, resulting in XAlgPEG hydrogels. XAlgPEG microbeads were formed by co-incubation of the two polymers, followed by ...
Farris Alton B AB - - 2010
In autoimmune pancreatitis (AIP), mechanism(s) of paradoxical glycemic control improvement (GCI) often occurring after pancreatic resection and steroid therapy are not fully elucidated. Using image quantitation, AIP cases (n = 10) with pre- and post-surgical glucose values were compared with chronic pancreatitis (CP) and normal pancreas (NP) regarding percent chromogranin ...
Yule David I DI Department of Pharmacology and Physiology, University of Rochester Medical School, Rochester, NY 14642, USA. David - - 2010
Pancreatic acinar cells are classical exocrine gland cells. The apical regions of clusters of coupled acinar cells collectively form a lumen which constitutes the blind end of a tube created by ductal cells - a structure reminiscent of a "bunch of grapes". When activated by neural or hormonal secretagogues, pancreatic ...
Wagner Ryan T RT Department of Molecular & Cellular Biology, Baylor College of Medicine, Houston, TX 77030, - - 2010
Type 1 diabetes is characterized by near total absence of pancreatic b cells. Current treatments consisting of insulin injections and islet transplantation are clinically unsatisfactory. In order to develop a cure for type 1 diabetes, we must find a way to reverse autoimmunity, which underlies b cell destruction, as well ...
Leja-Szpak Anna - - 2010
Pancreatic cancer is a highly lethal disease with a poor prognosis for long-term survival rate at all stages of invasiveness. It responds poorly to radio- and chemotherapy because the tumor cells are resistant to apoptosis. Melatonin has been reported to inhibit pancreatic cancer growth in experimental studies in animals but ...
Shimoda M - - 2010
It has been reported that the human pancreatic nonendocrine fraction, which remains after islet isolation, can be differentiated toward beta cells. However, the optimal method to accomplish this goal has not been established. In this study, we introduced the human neurogenic differentiation 1 (NeuroD1) gene into human nonendocrine pancreatic epithelial ...
Granata Riccarda - - 2010
The ghrelin gene peptides include acylated ghrelin (AG), unacylated ghrelin (UAG), and obestatin (Ob). AG, mainly produced by the stomach, exerts its central and peripheral effects through the GH secretagogue receptor type 1a (GHS-R1a). UAG, although devoid of GHS-R1a-binding affinity, is an active peptide, sharing with AG many effects through ...
Koblas T - - 2010
Adult pancreatic nonendocrine cells represent a potential alternative source of insulin-producing tissue for the treatment of diabetes. Differentiation of these cells is regulated by various signaling pathways including the phosphoinositide 3-kinase (PI3K) pathway. Therefore, we evaluated the effect of PI3K on this process. Compared with untreated cells the differentiation of ...
Noguchi H - - 2010
We previously established a mouse pancreatic stem cell line without genetic manipulation. In this study, we sought to identify and isolate human pancreatic stem/progenitor cells. We also tested whether growth factors and protein transduction of pancreatic and duodenal homeobox factor-1 (PDX-1) and BETA2/NeuroD into human pancreatic stem/progenitor cells induced insulin ...
Zhivkova-Galunska Maria - - 2010
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in western countries and among the malignancies with the worst prognosis. Osteonectin and osteopontin, two proteins of the extracellular matrix, have been found to be upregulated in PDAC. In the present study the expression of osteopontin mRNA as ...
Puff Ramona - - 2010
The members of the Suppressor of Cytokine Signaling (SOCS) protein family mainly modulate the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. SOCS-1 and SOCS-3 have already been shown to influence growth and apoptosis of pancreatic beta cells. We hypothesized that SOCS-2, which is expressed in pancreatic islets, ...
Béraud-Dufour Sophie - - 2010
Neurotensin (NT) is secreted from neurons and gastrointestinal endocrine cells. We previously reported that the three NT receptors (NTSRs) are expressed in pancreatic islets and beta cell lines on which we observed a protective effect of NT against cytotoxic agents. In this study, we explored the role of NT on ...
Puddu A - - 2010
Advanced Glycation End-Products (AGEs), a group of compounds resulting from the non-enzymatic reaction of reducing sugars with the free amino group of proteins, are implicated in diabetic complications. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T 15 to high concentrations of AGEs significantly decreases cell proliferation ...
Chamson-Reig A - - 2010
Transplantation of bone marrow-derived haemopoietic stem cells following streptozotocin (STZ) treatment to induce pancreatic beta cell loss in mice causes the partial regeneration of beta cell mass, with many haemopoietic cells demonstrating endothelial cell markers. This study used genetically tagged haemopoietic lineage-derived cells to determine how endogenous cells are mobilised ...
Shen H-C Jennifer - - 2010
The pancreatic alpha- and beta-cells are critical components in regulating blood glucose homeostasis via secretion of glucagon and insulin, respectively. Both cell types are typically localized in the islets of Langerhans. However, little is known about the roles of paracrine interactions that contribute to their physiological functions. The lack of ...
Blaine Stacy A - - 2010
Studies in both humans and rodents have found that insulin(+) cells appear within or near ducts of the adult pancreas, particularly following damage or disease, suggesting that these insulin(+) cells arise de novo from ductal epithelium. We have found that insulin(+) cells are continuous with duct cells in the epithelium ...
Itoh Masayuki - - 2010
Aristaless-related homeobox gene (ARX) mutation leads to several neurological disorders including X-linked lissencephaly with abnormal genitalia (XLAG), West syndrome and Partington syndrome, with XLAG being the most severe form. Although some of the brain pathologies of XLAG have already been described, the crucial extra-brain symptoms are severe growth retardation, transient ...
Wu Yuexiu - - 2010
Recent evidence has shown that stem cell factor (SCF) and its receptor, c-Kit, have an important role in pancreatic islet development by promoting islet cell differentiation and proliferation. In this study, we examined the role of c-Kit and SCF in the differentiation and proliferation of insulin- and glucagon-producing cells using ...
Fanjul Marjorie - - 2010
It has been shown that adult pancreatic ductal cells can dedifferentiate and act as pancreatic progenitors. Dedifferentiation of epithelial cells is often associated with the epithelial-mesenchymal transition (EMT). In this study, we investigated the occurrence of EMT in adult human exocrine pancreatic cells both in vitro and in vivo. Cells ...
Zhou Weidong - - 2010
Enolase is a key glycolytic enzyme that catalyzes the dehydration of 2-phosphoglycerate to phosphoenolpyruvate. Recently, enolase was revealed as an important protein in pathophysiological processes since it was found on the surface of hematopoietic cells and overexpressed in several tumor cells. Our previous studies demonstrated that alpha-enolase is up-regulated in ...
Inberg Alex - - 2010
Pancreatic beta-cells are vulnerable to multiple stresses, leading to dysfunction and apoptotic death. Deterioration in beta-cells function and mass is associated with type 2 diabetes. Comparative two-dimensional gel electrophoresis from pancreatic MIN6 cells that were maintained at varying glucose concentrations was carried out. An induced expression of a protein spot, ...
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