Pancreatic Cell News Volume 4.37 | Sep 24 2013

Functional Characteristics of Neonatal Rat Beta Cells with Distinct Markers
To study the acquisition of mature glucose-responsiveness, researchers compared glucose-regulated redox state, insulin synthesis and secretion of beta cells purified from neonatal or 10-week old rats to their transcriptomes and proteomes measured by oligonucleotide and LC-MS/MS profiling. [J Mol Endocrinol] Abstract

The Aryl Receptor Inhibitor Epigallocatechin-3-Gallate Protects INS-1E Beta-Cell Line against Acute Dioxin Toxicity
Researchers demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin is highly toxic for INS-1E cells, suggesting that pancreatic beta cells should be considered a relevant and sensitive target for dioxin acute toxicity. [Chemosphere] Abstract

Treatment with Glucokinase Activator, YH-GKA, Increases Cell Proliferation and Decreases Glucotoxic Apoptosis in INS-1 Cells
Scientists evaluated the proliferation and anti-apoptotic actions of YH-GKA, a novel and potent GKA, in INS-1 pancreatic β-cells. YH-GKA treatment increased cell numbers at 3 mM glucose via upregulation of insulin receptor substrate-2 and subsequent activation of AKT/protein kinase B phosphorylation. [Eur J Pharm Sci] Full Article

Pancreatic β Cell Proliferation by Intermittent Hypoxia via Up-Regulation of Reg Family Genes and HGF Gene
Intermittent hypoxia stress stimulates pancreatic β cell to induce interleukin (IL)-6 gene expression. By the IL-6 stimulation, β cells over-express regenerating gene (Reg) family genes as well as hepatocyte growth factor (HGF) gene. [Life Sci] Abstract

Extracellular Matrix-Mediated Differentiation of Human Embryonic Stem Cells: Differentiation to Insulin-Secreting Beta Cells
Decellularized extracellular-matrix and conditioned media from the appropriate committed cell lines are used to differentiate stem cells to the required phenotype. Applying this strategy to differentiate human embryonic stem cells to pancreatic beta cells, researchers obtained functional cells that secreted insulin in a glucose-responsive manner, and were able to recover normoglycemia in a streptozotocin-induced diabetic mouse model. [Tissue Eng Part A] Abstract

PANCREATIC CANCER

Inhibition of Amyloid Precursor Protein Processing Enhances Gemcitabine-Mediated Cytotoxicity in Pancreatic Cancer Cells
Researchers determined the role of Amyloid Precursor Protein (APP) in pancreatic cancer cell survival and proliferation. Their results show that pancreatic cancer cells secrete high levels of sAPP-alpha, the α-secretase cleaved ectodomain fragment of APP, as compared to normal non-cancerous cells. [J Biol Chem] Abstract | Full Article

PPAPDC1B and WHSC1L1 Are Common Drivers of the 8p11-12 Amplicon, Not Only in Breast Tumors but also in Pancreatic Adenocarcinomas and Lung Tumors
Researchers focused on cell lines derived from lung cancer and pancreatic adenocarcinoma and found a correlation between the amplification of PPAPDC1B and WHSC1L1 with their overexpression. Loss-of-function studies based on the use of siRNA and shRNA demonstrated that PPAPDC1B and WHSC1L1 played a major role in regulating the survival of pancreatic adenocarcinoma and small-cell lung cancer-derived cell lines. [Am J Pathol] Abstract

The Marine Natural Product Manzamine A Targets Vacuolar ATPases and Inhibits Autophagy in Pancreatic Cancer Cells
In pancreatic cancer cells, 10 µM manzamine A affected vacuolar ATPase activity and significantly increased the level of autophagosome marker LC3-II and p62/SQSTM1 as observed by western blot analysis. [Mar Drugs] Abstract | Full Article

Concomitant Targeting of Multiple Key Transcription Factors Effectively Disrupts Cancer Stem Cells Enriched in Side Population of Human Pancreatic Cancer Cells
Cancer stem cells were enriched in the side proportion cells contained in the human pancreatic cancer cell lines and they possessed aggressive growth, invasion, migration and drug-resistance properties, compared with non-side proportion cells. [PLoS One] Full Article

Emerging Targets in Pancreatic Cancer: Epithelial-Mesenchymal Transition and Cancer Stem Cells
There is emerging evidence that the epithelial-mesenchymal transition (EMT) process may give rise to cancer stem cells (CSCs), or at least cells with stem cell-like properties. The authors review the key pathways involved in both of these processes, the biomarkers used to identify CSCs, and new therapeutic approaches targeting CSCs and EMT in pancreatic ductal adenocarcinoma. [Onco Targets Ther] Abstract | Full Article

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Data Presented at EASD Support Safety Profile of Trajenta^® (Linagliptin) in Broad Range of Adults with Type 2 Diabetes
Boehringer Ingelheim and Eli Lilly and Company announced that results from two different pooled analyses of clinical studies support previous observations that the dipeptidyl peptidase-4 inhibitor linagliptin was shown to be well tolerated in a broad range of adults with Type 2 Diabetes. [Press release from Boehringer Ingelheim GmbH discussing research presented at the 49th Annual Meeting of the European Association for the Study of Diabetes (EASD), Barcelona] Press Release

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Harvard’s Wyss Institute and Charité, One of Europe’s Largest University Hospitals, Announce Partnership
The Wyss Institute for Biologically Inspired Engineering at Harvard University and Berlin-based Charité jointly announced a formal partnership. The announcement formalizes and elevates an existing collaboration between Wyss Core Faculty member David Mooney, Ph.D., and Georg Duda, Ph.D., Vice-Director of Charité’s Berlin-Brandenburg Center for Regenerative Therapies and Wyss Institute Associate Faculty member. [Hansjorg Wyss Institute for Biologically Inspired Engineering at Harvard University] Press Release

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Therapeutic Goods Administration (Australia)

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Postdoctoral Researcher – Molecular Mechanisms of Innate Immunity and Inflammation (University of North Carolina at Chapel Hill)

Postdoctoral Researcher – Pancreatic Cancer (UT Southwestern Medical Center at Dallas)

Postdoctoral Fellow – Molecular Mechanisms of Cardiovascular Diseases (University of Rochester Medical Center)

Postdoctoral Position – Mechanism of Pancreatic Beta Cell Proliferation (Joslin Diabetes Center/Harvard Medical School)

Postdoctoral Fellow – Pancreatic Beta Cell Regeneration and Survival (Oklahoma Medical Research Foundation)

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

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Technologist – Mesenchymal Cell Research (STEMCELL Technologies Inc.)

Research Technologist – Cell Culture Media & Matrices (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

Quality Control Analyst – Media (STEMCELL Technologies Inc.)

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