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Demeterco C - - 2009
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 ...
Oliver Nick - - 2009
The normal pancreatic beta-cell membrane depolarizes in response to increasing concentrations of glucose in a bursting pattern. At <7 mM (126 mg/dl), the cell is electrically silent. The bursting pulse width increases as glucose rises >7 mM (126 mg/dl) until a continuous train of bursting is seen at >25 mM ...
Thiago L S - - 2010
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is the most common malignancy in children. The Wnt signaling pathway has been found to be extensively involved in cancer onset and progression but its role in BCP-ALL remains controversial. We evaluate the role of the Wnt pathway in maintenance of BCP-ALL cells and ...
Guettier Jean-Marc JM Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. - - 2009
Impaired functioning of pancreatic beta cells is a key hallmark of type 2 diabetes. beta cell function is modulated by the actions of different classes of heterotrimeric G proteins. The functional consequences of activating specific beta cell G protein signaling pathways in vivo are not well understood at present, primarily ...
Cnop M M Laboratory of Experimental Medicine and Division of Endocrinology, Université Libre de Bruxelles, Brussels, - - 2010
Defects in pancreatic beta cell turnover are implicated in the pathogenesis of type 2 diabetes by genetic markers for diabetes. Decreased beta cell neogenesis could contribute to diabetes. The longevity and turnover of human beta cells is unknown; in rodents <1 year old, a half-life of 30 days is estimated. ...
Sachdeva Mira M - - 2009
Type 2 diabetes mellitus (T2DM) results from pancreatic beta cell failure in the setting of insulin resistance. Heterozygous mutations in the gene encoding the beta cell transcription factor pancreatic duodenal homeobox 1 (Pdx1) are associated with both T2DM and maturity onset diabetes of the young (MODY4), and low levels of ...
Saisho Y Y Larry Hillblom Islet Research Center, UCLA David Geffen School of Medicine, Los Angeles, CA 90024-2852, - - 2010
We sought to establish the relationship between fasting plasma glucose concentrations and pancreatic fractional beta cell area in adult cynomolgus monkeys (Macaca fascicularis). Fasting plasma glucose and pancreatic fractional beta cell area were measured in 18 control and 17 streptozotocin-treated adult primates (17.0 +/- 1.2 vs 15.4 +/- 1.2 years ...
Lacraz Grégory - - 2010
The alteration of the beta-cell population in the Goto-Kakizaki rat (GK/Par line), a model of spontaneous type 2 diabetes, has been ascribed to significantly decreased beta-cell replication and neogenesis, while beta-cell apoptosis is surprisingly not enhanced and remains in the normal range. To gain insight into the mechanisms by which ...
Kim Ji-Won - - 2009
The pathogenesis of post-transplant diabetes mellitus (PTDM) is thought to be partly related to the direct toxic effect of cyclosporine (CsA) on pancreatic beta-cells and the resultant decrease in insulin synthesis and secretion. Although rosiglitazone (Rosi) is an insulin sensitizer, recent data has shown that Rosi also directly protects against ...
Zhang Hongjie - - 2010
The objectives of the study were to determine whether the cell cycle transcription factor, FoxM1, is required for glucose homeostasis and beta-cell mass expansion in maternal islets during pregnancy and whether FoxM1 is essential for placental lactogen (PL)-induced beta-cell proliferation. beta-Cell mass, beta-cell proliferation, and glucose homeostasis were assessed in ...
Hennige Anita M - - 2010
In vitro models suggest that free fatty acid-induced apoptotic beta-cell death is mediated through protein kinase C (PKC)delta. To examine the role of PKCdelta signaling in vivo, transgenic mice overexpressing a kinase-negative PKCdelta (PKCdeltaKN) selectively in beta-cells were generated and analyzed for glucose homeostasis and beta-cell survival. Mice were fed ...
Ino Kosuke - - 2009
Endocrine disruptors that act like hormones in the endocrine system might have toxic effects. Therefore, it is important to develop a portable device that can detect hormone active chemicals in samples rapidly and easily. In this study, a microfluidic device was developed for the detection of hormone active chemicals using ...
Ebihara Nobuyuki - - 2009
PURPOSE: To investigate the expression and function of fibroblast growth factor-inducible 14 (Fn14) in human retinal pigment epithelial cells. METHODS: A human retinal pigment epithelial cell line (RPE cells: ARPE-19) was used. Expression of Fn14 protein was assessed by flow cytometry. An antibody array and ELISA were used to detect ...
Baeyens Luc - - 2009
Cell replacement therapy holds promises for treatment of patients suffering from diabetes mellitus. When determining the appropriate strategies to amplify the amount of transplantable beta-cells, sufficient knowledge of the developmental programs regulating beta-cell differentiation is crucial. Here, we describe the plasticity of the different pancreatic cell types in vivo and ...
Fu Accalia A Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, - - 2009
The Lkb1 tumor suppressor exerts its biological effects through phosphorylation and consequent activation of the AMP kinase (AMPK) family. Extensive genetic and biochemical evidence supports a role for Lkb1 in cell cycle arrest, establishment of cell polarity, and cellular energy metabolism. However, the role of Lkb1 and the AMPK family ...
Granot Zvi Z Department of Developmental Biology and Cancer Research and Molecular Biology, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem 91120, - - 2009
Pancreatic beta cells, organized in the islets of Langerhans, sense glucose and secrete appropriate amounts of insulin. We have studied the roles of LKB1, a conserved kinase implicated in the control of cell polarity and energy metabolism, in adult beta cells. LKB1-deficient beta cells show a dramatic increase in insulin ...
Nakamura Shin-Ichi - - 2010
Transforming growth factor-betas (TGF-betas), expressed in various tissues, play important roles in embryonic development and adult tissue homeostasis through their effects on cell proliferation, cell differentiation, cell death, and cell motility. However, expression of TGF-beta signaling components and their biological effect on taste epithelia has not been elucidated. We performed ...
Liu Xin - - 2010
BACKGROUND AND AIMS: Compound Astragalus and Salvia miltiorrhiza extract (CASE) is made up of astragalosides, astragalus polysaccharide and salvianolic acids extracted from Astragalus membranaceus Bunge (Leguminosae) and Salvia miltiorhiza Bunge (Lamiaceae) with a standard ratio. Previous reports showed that CASE inhibited hepatic fibrosis by mediating transforming growth factor (TGF)-beta/Smad signaling. ...
Glauser Dominique A - - 2009
Lack of nutrients and growth factors activates FoxO transcription factors in pancreatic beta-cells, whereas PI3K/Akt-dependent inactivation of FoxO favors proliferation. To address the link between FoxO and cell cycle control, we deprived Min6 cells of serum and glucose which activated FoxO and inhibited proliferation. Concomitantly, expression of the transcriptional repressor ...
Borowiak Malgorzata M Harvard Stem Cell Institute, Department of Stem Cell and Regeneration Biology, Harvard University, Cambridge, MA 02138, USA. - - 2009
Insulin-producing beta cells are lost or insufficient in diabetic patients, presenting the medical challenge for new beta cells. Currently, there are three strategies that offer promise. One involves the generation of beta cells de novo by directing the differentiation of either embryonic stem cells or induced pluripotent cells to the ...
Chen Zhi-hong - - 2009
BACKGROUND: Islet beta-cells are almost completely destroyed when patients with type 1 diabete are diagnosed. To date, insulin substitute therapy is still one of the main treatments. The cure of type 1 diabetes requires beta-cell regeneration from islet cell precursors and prevention of recurring autoimmunity. Therefore, beta-cell regeneration and proliferation ...
Liu Moyan - - 2010
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease that exclusively progresses to renal failure. An important target for the treatment of ADPKD is to reduce cystic cell proliferation. PPARγ agonists such as TZDs are insulin sensitizing agents that have also been reported to decrease tumor growth. Here we ...
Li J - - 2010
The reduction in insulin secretory capacity and beta-cell mass has been attributed, at least partially, to lipotoxicity, which may contribute to the development of type 2 diabetes. Chronic free fatty acids (FFA) exposure impairs pancreatic beta-cell function and induces beta-cell apoptosis. This study is to elucidate the underlying molecular mechanisms. ...
Gibbs John D JD Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, - - 2009
Respiratory syncytial virus (RSV) is a common respiratory viral infection in children which is associated with immune dysregulation and subsequent induction and exacerbations of asthma. We recently reported that treatment of primary human epithelial cells (PHBE cells) with transforming growth factor beta (TGF-beta) enhanced RSV replication. Here, we report that ...
García Mónica - - 2009
Enteroviral infections are associated with type I diabetes. The mechanisms by which viruses or viral products such as double-stranded RNA (dsRNA) affect pancreatic beta cell function and survival remain unclear. We have shown that extracellular dsRNA induces beta cell death via Toll-like receptor-3 (TLR3) signaling whereas cytosolic dsRNA triggers the ...
Cooperberg Benjamin A - - 2009
Given evidence of both indirect and direct signaling, we tested the hypothesis that increased beta-cell-mediated signaling of alpha-cells negates direct alpha-cell signaling in the regulation of glucagon secretion in humans. We measured plasma glucagon concentrations before and after ingestion of a formula mixed meal and, on a separate occasion, ingestion ...
Panasyuk Ganna - - 2009
The mTOR (mammalian target of rapamycin) promotes growth in response to nutrients and growth factors and is deregulated in numerous pathologies, including cancer. The mechanisms by which mTOR senses and regulates energy metabolism and cell growth are relatively well understood, whereas the molecular events underlining how it mediates survival and ...
Guney Michelle A - - 2009
Diabetes is characterized by decreased function of insulin-producing beta cells and insufficient insulin output resulting from an absolute (Type 1) or relative (Type 2) inadequate functional beta cell mass. Both forms of the disease would greatly benefit from treatment strategies that could enhance beta cell regeneration and/or function. Successful and ...
Maehr René R Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, - - 2009
Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic beta cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be ...
Natale David R C DR Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, The University of Calgary, Calgary, AB, Canada T2N 4N1. - - 2009
Prolonged maintenance of trophoblast stem (TS) cells requires fibroblast growth factor (FGF) 4 and embryonic fibroblast feeder cells or feeder cell-conditioned medium. Previous studies have shown that TGF-beta and Activin are sufficient to replace embryonic fibroblast-conditioned medium. Nodal, a member of the TGF-beta superfamily, is also known to be important ...
Hesselson Daniel - - 2009
Pancreatic beta-cells are critical regulators of glucose homeostasis, and they vary dramatically in their glucose stimulated metabolic response and levels of insulin secretion. It is unclear whether these parameters are influenced by the developmental origin of individual beta-cells. Using HOTcre, a Cre-based genetic switch that uses heat-induction to precisely control ...
Hardy Alexandre B - - 2009
Voltage-gated eag-related gene (Erg) K(+) channels regulate the electrical activity of many cell types. Data regarding Erg channel expression and function in electrically excitable glucagon and insulin producing cells of the pancreas is limited. In the present study Erg1 mRNA and protein were shown to be highly expressed in human ...
Mori Hiroyuki - - 2009
TSC1 is a tumor suppressor that associates with TSC2 to inactivate Rheb, thereby inhibiting signaling by the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). mTORC1 stimulates cell growth by promoting anabolic cellular processes, such as translation, in response to growth factors and nutrient signals. To test roles for TSC1 ...
Collombat Patrick P Department of Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, Am Fassberg, D-37077 Göttingen, Germany. - - 2009
We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-specific promoters and demonstrate ...
Hajduskova Martina - - 2009
Asymmetric cell divisions produce new cell types during animal development. Studies in Caenorhabditis elegans have identified major signal-transduction pathways that determine the polarity of cell divisions. How these relatively few conserved pathways interact and what modulates them to ensure the diversity of multiple tissue types is an open question. The ...
Susick Laura - - 2009
The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) has recently been shown to inhibit deleterious effects of cytokines on beta-cells, but it is unable to protect beta-cells from death due to its own cytotoxicity. Herein, we investigated novel HDAC inhibitors for their cytoprotective effects against IL-1beta-induced damage to isolated beta-cells. ...
Susick Laura L Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, - - 2009
The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) has recently been shown to inhibit deleterious effects of cytokines on beta-cells, but it is unable to protect beta-cells from death due to its own cytotoxicity. Herein, we investigated novel HDAC inhibitors for their cytoprotective effects against IL-1beta-induced damage to isolated beta-cells. ...
de Miguel-Santos Laura - - 2010
Replication, neogenesis, and apoptosis play a main role in neonatal endocrine pancreas remodeling. IGFs are major contributors to beta-cell growth and function and are highly sensitive to nutritional status. We previously showed that maternal malnutrition caused an increase in beta-cell mass in fetuses related to the stimulation of beta-cell proliferation ...
Shiau Rong-Jen - - 2010
BACKGROUND: The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy and decreasing the toxicity of chemotherapy. However, whether nutritional factors enhance the effect of trichostatin A (TSA), a novel anti-cancer drug, is unclear. AIM: We investigated the individual enhancing effect and its possible ...
Dugina Vera - - 2009
Using newly generated monoclonal antibodies, we have compared the distribution of beta- and gamma-cytoplasmic actin in fibroblastic and epithelial cells, in which they play crucial roles during various key cellular processes. Whereas beta-actin is preferentially localized in stress fibers, circular bundles and at cell-cell contacts, suggesting a role in cell ...
Li Changgong - - 2009
The precise mechanisms by which beta-catenin controls morphogenesis and cell differentiation remain largely unknown. Using embryonic lung development as a model, we deleted exon 3 of beta-catenin via Nkx2.1-cre in the Catnb[+/lox(ex3)] mice and studied its impact on epithelial morphogenesis. Robust selective accumulation of truncated, stabilized beta-catenin was found in ...
Shaykhalishahi Hamed - - 2009
Alzheimer's disease is the major cause of senile dementia with the hallmark of beta-amyloid deposition in neurons. Although the main cause(s) of this deposition is not fully understood, however, the wealth of the present literature data supports the pivotal role of reactive oxygen and nitrogen species in both the initiation ...
Gwak Jungsug - - 2009
Aberrant accumulation of intracellular beta-catenin in intestinal epithelial cells is a frequent early event during the development of colon cancer. To identify small molecules that decrease the level of intracellular beta-catenin, we performed cell-based chemical screening using genetically engineered HEK293 reporter cells to detect compounds that inhibit TOPFlash reporter activity, ...
Estil les Elisabet - - 2009
Interleukin-1beta (IL1B) is an important contributor to the autoimmune destruction of beta-cells in type 1 diabetes, and it has been recently related to the development of type 2 diabetes. IGF2 stimulates beta-cell proliferation and survival. We have determined the effect of IL1B on beta-cell replication, and the potential modulation by ...
Filhoulaud Gaëlle - - 2009
Pancreatic exocrine and endocrine cells develop during embryonic life from endodermal progenitors. This process depends on activation of a hierarchy of transcription factors. Although information is available regarding the mesodermal signals controlling pancreas development, little is known about the role of environmental factors such as nutrients, including glucose, that also ...
Bertran Esther - - 2009
Treatment of FaO rat hepatoma cells with TGF-beta selects cells that survive to its apoptotic effect and undergo epithelial-mesenchymal transitions (EMT). We have established a cell line (T beta T-FaO, from TGF-beta-treated FaO) that shows a mesenchymal, de-differentiated, phenotype in the presence of TGF-beta and is refractory to its suppressor ...
Kim Dongkyun - - 2009
Endochondral ossification is characterized by a significant interdependence between cell shape and cytoskeletal organization that accompanies the onset of chondrogenic signaling. However, the mechanisms mediating these interactions have not been well studied. Here, treatment with transforming growth factor (TGF)-beta3 at a later stage of chondrogenesis led to activation of Smad-2 ...
Li Qingdi Q - - 2009
beta-Elemene, a new plant-derived anticancer agent with low toxicity, has been reported to be effective in the treatment of leukemia and solid tumors. In the current study, we explored the therapeutic application of beta-elemene in sensitizing lung cancer cells to cisplatin. beta-Elemene considerably enhanced the inhibitory effect of cisplatin on ...
Hasegawa Takuto - - 2009
Two kinds of rhodamine modified beta-cyclodextrins (R-1 and R-2), which are coupled up ethylene diamine (EDA) and tetraethylene pentamine (TEPA) between Rh B and beta-cyclodextrin, respectively, have been synthesized. R-1 and 2 work as a new fluorogenic probe for monitoring pH of Hela cells, and MTT of assay R-1, R-2, ...
Park Miejung - - 2009
Enterostatin is a peptide that regulates dietary fat intake in rodents and inhibits insulin secretion from pancreatic beta cells. Microarray studies of the genomic response of both a human hepatoma cell line (HepG2 cells) and a mouse hypothalamic cell line (GT1-7 cells) to enterostatin suggested that it might regulate protein ...
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