Pancreatic Cell News Volume 6.13 | Apr 7 2015

Metformin Activates Duodenal AMPK and a Neuronal Network to Lower Glucose Production
Researchers showed that intraduodenal infusion of metformin for 50 min activated duodenal mucosal AMP-activated protein kinase (AMPK) and lowered hepatic glucose production in a rat three day high fat diet-induced model of insulin resistance. [Nat Med] Abstract | Press Release

Epigenetic Priming of Enhancers Predicts Developmental Competence of hESC-Derived Endodermal Lineage Intermediates
Investigators report that epigenetic priming of enhancers signifies developmental competence during endodermal lineage diversification. Chromatin mapping during pancreatic and hepatic differentiation of human embryonic stem cells revealed the en masse acquisition of a poised chromatin state at enhancers specific to endoderm-derived cell lineages in gut tube intermediates. [Cell Stem Cell]
Abstract | Graphical Abstract | Press Release

Insm1 Cooperates with Neurod1 and Foxa2 to Maintain Mature Pancreatic β-Cell Function
The authors showed that Insm1, Neurod1 and Foxa2 directly interacted and together bind regulatory sequences in the genome of mature pancreatic β-cells. They used Insm1 ablation in mature β-cells in mice and found pronounced deficits in insulin secretion and gene expression. [EMBO J] Full Article | Graphical Abstract

Glucose Tolerance Is Improved in Mice Invalidated for the Nuclear Receptor HNF-4 Gamma: A Critical Role for Enteroendocrine Cell Lineage
GLP-1 exerted a trophic effect on pancreatic β-cells and researchers report an increase of the β-cell fraction correlated with an augmented number of proliferative islet cells and with resistance to streptozotocin-induced diabetes. [Diabetes] Abstract

Inducible VEGF Expression by Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Reduces the Minimal Islet Mass Required to Reverse Diabetes
Scientists hypothesized that co-transplantation of islets with human embryonic stem cell-derived mesenchymal stromal cells that conditionally overexpress VEGF may augment islet revascularization and reduce the minimal islet mass required to reverse diabetes in mice. [Sci Rep] Full Article

Redox Signal-Mediated Enhancement of the Temperature Sensitivity of Transient Receptor Potential Melastatin 2 (TRPM2) Elevated Glucose-Induced Insulin Secretion from Pancreatic Islets
Researchers focused on the physiological functions of redox signal-mediated transient receptor potential melastatin 2 (TRPM2) activity at body temperature. H₂O₂, an important molecule in redox signaling, reduced the temperature threshold for TRPM2 activation in pancreatic β-cells of wild-type mice, but not in TRPM2KO cells. [J Biol Chem] Abstract | Full Article

PANCREATIC CANCER

Microenvironmental hCAP-18/LL-37 Promotes Pancreatic Ductal Adenocarcinoma by Activating Its Cancer Stem Cell Compartment
Treatment of pancreatic cancer stem cells with recombinant LL-37 increased pluripotency-associated gene expression, self-renewal, invasion and tumorigenicity via formyl peptide receptor 2- and P2X purinoceptor 7 receptor-dependent mechanisms, which could be reversed by inhibiting these receptors. [Gut] Abstract

Ormeloxifene Suppresses Desmoplasia and Enhances Sensitivity of Gemcitabine in Pancreatic Cancer
Researchers report for the first time that a nonsteroidal drug, ormeloxifene (ORM), has potent anti-cancer properties and depletes tumor-associated stromal tissue by inhibiting the sonic hedgehog signaling pathway in pancreatic ductal adenocarcinoma (PDAC). They found that ORM inhibited cell proliferation and induced death in PDAC cells, which provoked them to investigate the combinatorial effects of ORM with gemcitabine at the molecular level. [Cancer Res] Abstract

Omeprazole Inhibits Pancreatic Cancer Cell Invasion through a Non-Genomic Aryl Hydrocarbon Receptor Pathway
Treatment of highly invasive Panc1 pancreatic cancer cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), omeprazole and seven other AhR-active pharmaceuticals showed that only omeprazole and tranilast but not TCDD inhibited invasion in a Boyden chamber assay. [Chem Res Toxicol] Abstract

Effects of Ropivacaine, Bupivacaine and Sufentanil in Colon and Pancreatic Cancer Cells In Vitro
Scientists investigated the effects of the clinically used local anesthetics ropivacaine or bupivacaine and the opioid analgesic sufentanil on cell proliferation, cell cycle distribution and apoptosis of colon and pancreatic cancer cell lines in vitro. [Pharmacol Res] Abstract

Superoxide Dismutase Promotes the Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells via Activation of the H₂O₂/ERK/NF-κB Axis
Scientists evaluated whether superoxide dismutase (SOD) affects epithelial-mesenchymal transition in pancreatic cancer cells and the related mechanism. Human pancreatic cancer cells BxPC-3 and Panc-1 were utilized to examine the level of hydrogen peroxide in the absence or presence of SOD and catalase. [Int J Oncol] Abstract

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Zebrafish Accelerate TGen Research against Pancreatic Cancer
Scientists at the Translational Genomics Research Institute (TGen) are using zebrafish to accelerate investigations of pancreatic cancer. TGen researchers believe the zebrafish can aid in the search for therapeutics that could help slow down, and even reverse, the growth and spread of cancer in pancreatic cancer patients. [Translational Genomics Research Institute] Press Release

Myriad and AstraZeneca Expand Research Collaboration on Lynparza
Myriad Genetics, Inc. announced the expansion of its companion diagnostic collaboration with AstraZeneca. Under the terms of the expanded agreement, Myriad’s BRACAnalysis CDx test will be used to prospectively identify which patients with metastatic pancreatic cancer may respond to treatment with Lynparza^™ (olaparib). [Myriad Genetics, Inc.] Press Release

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NEW Research Assistant Professor – Protein Misfolding and Toxicity (George Washington University)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Director – Center of Emphasis in Diabetes and Metabolism (Texas Tech University Health Sciences Center)

Postdoctoral Position – Type 2 Diabetes, Obesity, and Metabolism (Boston Children’s Hospital)

Postdoctoral Position – Obesity & Diabetes (INSERM U892)

PhD Position – Lineage Reprogramming (Max Delbrück Center for Molecular Medicine)

Postdoctoral Positions – Developmental Biology (Joslin Diabetes Center)

Postdoctoral Fellow – Type 2 Diabetes (Harvard Medical School)

Tenure-Track Immunology Faculty Position – Diabetes (University of Connecticut Health Center)

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