Volume 4.24 | Jun 25

Pancreatic Cell News 4.24 June 25, 2013
     In this issue: Publications | ReviewsScience News | Industry News | Policy News | Events | Jobs 
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TOP STORY
Metabolic Regulation of Cellular Plasticity in the Pancreas
Investigators employed the fluorescent ubiquitination-based cell-cycle indicator system to investigate ß cell replication in real time and found that high nutrient concentrations induce rapid ß cell proliferation. Importantly, they found that high nutrient concentrations also stimulate ß cell differentiation from progenitors in the intrapancreatic duct. [Curr Biol] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

DIABETES

PDX1 in Ducts Is Not Required for Postnatal Formation of ß-Cells but Is Necessary for Their Subsequent Maturation
Pancreatic duodenal homeobox-1 (Pdx1), a transcription factor required for pancreatic development and maintenance of ß-cell function, was assessed for a possible role in postnatal ß-cell formation from progenitors in the pancreatic ducts by selectively deleting Pdx1 from the ducts. [Diabetes] Abstract

Consequences of Exposure to Light at Night on the Pancreatic Islet Circadian Clock and Function in Rats
Researchers validated the use of Per-1:LUC transgenic rats for continuous longitudinal assessment of islet circadian clock function ex vivo. Using this methodology, they subsequently examined effects of the continuous exposure to light at night on islet circadian clock and insulin secretion in vitro in rat islets. [Diabetes] Abstract

The Loss of Sirt1 in Mouse Pancreatic Beta Cells Impairs Insulin Secretion by Disrupting Glucose Sensing
Researchers aimed to determine how Sirtuin 1 (SIRT1) regulates insulin secretion in the pancreatic beta cell. OGTTs showed impaired glucose disposal in Sirt1BKO mice due to insufficient insulin secretion. [Diabetologia] Abstract

Coxsackievirus B4 Can Infect Human Pancreas Ductal Cells and Persist in Ductal-Like Cell Cultures which Results in Inhibition of Pdx1 Expression and Disturbed Formation of Islet-Like Cell Aggregates
The infection of human pancreas ductal cells and pancreatic duct cell line, PANC-1, with Coxsackievirus B (CVB)4E2 was studied. Primary ductal cells and PANC-1 cells were infectable with CVB4E2 and a RT-PCR assay without extraction displayed that a larger proportion of cells harbored viral RNA than predicted by the detection of the viral capsid protein VP1 by indirect immunofluorescence. [Cell Mol Life Sci] Abstract

PPAR? and Its Target Genes Are Downstream Effectors of FoxO1 in Islet Beta-Cells: Mechanism of Beta-Cell Compensation and Failure
Scientists used in vitro and in vivo systems to show that FoxO1, an integrator of metabolic stimuli, inhibits PPAR? expression in beta-cells, thus transcription of its target genes that are important regulators of beta-cell function, survival, and compensation. [J Biol Chem] Abstract | Full Article

PANCREATIC CANCER

Isolation, Culture and Genetic Manipulation of Mouse Pancreatic Ductal Cells
Scientists describe a protocol for isolating mouse pancreatic ductal epithelial cells and ductlike cells directly in vivo using ductal-specific Dolichos biflorus agglutinin lectin labeling followed by magnetic bead separation. Isolated cells can be cultured, manipulated by lentiviral transduction to modulate gene expression and directly used for molecular studies. [Nat Protoc] Abstract

Inhibition of Protein Phosphatase 2A Radiosensitizes Pancreatic Cancers by Modulating CDC25C/CDK1 and Homologous Recombination Repair
Researchers determined the effect of protein phosphatase 2A (PP2A) inhibition by genetic and pharmacological approaches on radiosensitization of Panc-1 and MiaPaCa-2 pancreatic cancer cells both in vitro and in vivo. PPP2R1A depletion by siRNA radiosensitized Panc-1 and MiaPaCa-2 cells, with radiation enhancement ratios of 1.4. [Clin Cancer Res] Abstract

Hedgehog Signaling Regulates Hypoxia Induced Epithelial to Mesenchymal Transition and Invasion in Pancreatic Cancer Cells via a Ligand-Independent Manner
Researchers investigated the role of Hedgehog (Hh) signaling in hypoxia induced pancreatic cancer epithelial to mesenchymal transition (EMT) and invasion. They showed that non-canonical Hh signaling is required as an important role to switch on hypoxia-induced EMT and invasion in pancreatic cancer cells. [Mol Cancer] Abstract | Full Article

An iPSC Line from Human Pancreatic Ductal Adenocarcinoma Undergoes Early to Invasive Stages of Pancreatic Cancer Progression
Researchers hypothesized that if human pancreatic ductal adenocarcinoma (PDAC) cells were converted to pluripotency and then allowed to differentiate back into pancreatic tissue, they might undergo early stages of cancer. Although most induced pluripotent stem cell (iPSC) lines were not of the expected cancer genotype, one PDAC line, 10-22 cells, when injected into immunodeficient mice, generated pancreatic intraepithelial neoplasia precursors to PDAC that progressed to the invasive stage. [Cell Rep]
Abstract | Graphical Abstract | Full Article | Press Release

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REVIEWS

Islet Inflammation: A Unifying Target for Diabetes Treatment?
In the past decade, islet inflammation has emerged as a contributor to the loss of functional ß cell mass in both type 1 and type 2 diabetes. Evidence supports the idea that overnutrition and insulin resistance result in the production of proinflammatory mediators by ß cells. [Trends Endocrin Met] Abstract

Pathophysiological Mechanisms Involving Aggressive Islet Cell Destruction in Fulminant Type 1 Diabetes
This review summarizes new findings related to the pathophysiology of accelerated ß-cell failure in fulminant type 1 diabetes. [Endocr J] Abstract | Full Article

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.

SCIENCE NEWS

Phase III Data Show Investigational Compound Empagliflozin Reduced Blood Glucose in Adults with Type 2 Diabetes Treated with Basal Insulin
Boehringer Ingelheim and Eli Lilly and Company announced results of a 78-week Phase III clinical trial of the investigational compound empagliflozin as an add-on to basal insulin in people with Type 2 Diabetes. [Press release from Boehringer Ingelheim GmbH discussing research presented at the American Diabetes Association® 73rd Scientific Sessions, Chicago] Press Release

Isis Reports Phase II Data on ISIS-APOCIII Rx Showing Significant Reductions in Triglycerides and APOC-III in Patients with High Triglycerides and Type 2 Diabetes
Isis Pharmaceuticals, Inc. announced that data from the Phase II study of ISIS-APOCIIIRx in patients with high triglycerides and type 2 diabetes were presented . [Press release from Isis Pharmaceuticals, Inc. discussing research presented at the American Diabetes Association® 73rd Scientific Sessions, Chicago] Press Release

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INDUSTRY NEWS

JDRF Announces Two Partnerships to Develop Stable, Pumpable Glucagon to Support Advanced Generation Artificial Pancreas Systems
JDRF announced partnerships with both Xeris Pharmaceuticals, Inc., and LATITUDE Pharmaceuticals, Inc., to support the development of soluble glucagon formulations-an important step toward the advancement of future generation, fully automated and multi-hormonal artificial pancreas systems for people with type 1 diabetes. [JDRF] Press Release

JDRF Extends Collaboration with BD to Develop Combined Infusion and Monitoring Products for People with Type 1 Diabetes
JDRF and BD are accelerating the development of new products that combine BD’s proprietary insulin infusion and glucose sensing technologies through a new collaboration. This new, three-year commitment is an extension of existing JDRF-BD collaborations focused on type 1 diabetes. [BD] Press Release

POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)
 
Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS

NEW World Conference on Regenerative Medicine
October 23-25, 2013
Leipzig, Germany

Visit our events page to see a complete list of events in the pancreatic cell community.

JOB OPPORTUNITIES

NEW Research Associate, Senior – Pancreatic Cancer (James Graham Brown Cancer Center)

Postdoctoral Research Fellow – Platelet Biology and Diabetes (Thomas Jefferson University, Cardeza Foundation for Hematologic Research)

Postdoctoral Researcher – Experimental Diabetes and Protein Research (Lund University/Experimental Medical Science)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Diabetes UK PhD Studentship (Diabetes UK)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

PhD Positions – Molecular Mechanisms Controlling Acinar Cell Proliferation (University Hospital Zuerich)

Postdoctoral Researcher (The University of Texas Health Science Center at San Antonio)


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