Volume 4.11 | Mar 26

Pancreatic Cell News 4.11 March 26, 2013
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs 
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TOP STORY
Lysine-5 Acetylation Negatively Regulates Lactate Dehydrogenase A and Is Decreased in Pancreatic Cancer
Researchers showed that lactate dehydrogenase A (LDH-A) is acetylated at lysine 5 (K5) and that this acetylation inhibits LDH-A activity. Replacement of endogenous LDH-A with an acetylation mimetic mutant decreases cell proliferation and migration. Importantly, K5 acetylation of LDH-A is reduced in human pancreatic cancers. Their study reveals a mechanism of LDH-A upregulation in pancreatic cancers. [Cancer Cell] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

DIABETES

Otubain 2 Is a Novel Promoter of Beta Cell Survival as Revealed by siRNA High-Throughput Screens of Human Pancreatic Islets
Pro-inflammatory cytokines induce death of beta cells and hamper engraftment of transplanted islet mass. Investigators aimed to reveal novel genes involved in this process, as a platform for innovative therapeutic approaches. Small interfering RNA (siRNA) high-throughput screening of primary human islets was employed to identify novel genes involved in cytokine-induced beta cell apoptosis. [Diabetologia] Abstract

LIM-Homeodomain Transcription Factor Isl-1 Mediates the Effect of Leptin on Insulin Secretion in Mice
Researchers showed that all leptin target cells in pancreatic islets and NIT beta cell express Isl-1. Both in vivo and in vitro results demonstrate that leptin suppresses Isl-1 expression and insulin secretion in islet in physiological and patho-physiological condition e.g., high fat diet. [J Biol Chem] Abstract | Full Article

The Adult Mammalian Pancreas Contains Separate Precursors of Pancreatic and Neural Crest Developmental Origins
Previously, lineage tracing experiments showed that multipotent precursors in mouse islets had a pancreatic and not a neural crest developmental origin. However, a different Cre reporter system reveals that there is a rare population of proliferative cells in the pancreas that is descended from the Wnt1 neural crest lineage, in addition to the majority population descended from the Pdx1 pancreatic lineage. [Stem Cells Dev] Abstract

The Complex Effects of Cannabinoids on Insulin Secretion from Rat Isolated Islets of Langerhans
A variety of purported cannabinoid CB receptor agonists and antagonists were evaluated for their effects on insulin secretion. In fresh rat isolated islets, the endocannabinoid anandamide caused a glucose-dependent, concentration-dependent inhibition of insulin release, with two populations of islets being identified based on their sensitivity to anandamide. [Eur J Pharmacol] Abstract

Pancreatic Stellate Cells Reduce Insulin Expression and Induce Apoptosis in Pancreatic β-Cells
Investigators hypothesized that pancreatic stellate cells (PSCs) might affect the phenotype of pancreatic β-cells. α-Smooth muscle actin (a marker of activated PSC)-positive cells were found within and around the fibrotic islets. [Biochem Biophys Res Commun] Abstract

PANCREATIC CANCER

Pancreatic Cancer Associated Stellate Cells Promote Differentiation of Myeloid-Derived Suppressor Cells in a STAT3-Dependent Manner
Scientists hypothesized that factors produced by human pancreatic stellate cells could enhance myeloid-derived suppressor cell differentiation and function, which promotes an immunosuppressive microenvironment. [Cancer Res] Abstract

Palladin Promotes Invasion of Pancreatic Cancer Cells by Enhancing Invadopodia Formation in Cancer-Associated Fibroblasts
Researchers utilized immortalized human pancreatic cancer-associated fibroblasts (CAFs) to investigate molecular pathways that control the matrix-remodeling and invasion-promoting activity of CAFs. In mouse xenograft experiments using a mixture of CAFs and tumor cells, palladin expression in CAFs promoted the rapid growth and metastasis of human pancreatic tumor cells. [Oncogene] Abstract | Press Release

Six1 Promotes Proliferation of Pancreatic Cancer Cells via Upregulation of Cyclin D1 Expression
Scientists showed that the relative expression of Six1 mRNA is increased in pancreatic cancer and correlated with advanced tumor stage. In vitro functional assays demonstrated that forced overexpression of Six1 significantly enhances the growth rate and proliferation ability of pancreatic cancer cells. [PLoS One]
Full Article

Induction of Pancreatic Cancer Cell Apoptosis, Invasion, Migration, and Enhancement of Chemotherapy Sensitivity of Gemcitabine, 5-FU, and Oxaliplatin by hnRNP A2/B1 siRNA
Researchers investigated the effects of inhibiting heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) expression on apoptosis, invasion, migration, and the chemotherapy sensitivity of pancreatic cancer cells to gemcitabine, 5-FU, and oxaliplatin chemotherapy using small interfering RNA (siRNA). [Anticancer Drugs] Abstract

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REVIEWS

The Role of Protein Synthesis and Digestive Enzymes in Acinar Cell Injury
This review focuses on protein synthesis and active digestive enzymes-two key stressors faced by the acinar cell that are likely to be the major drivers of pathology encountered in the pancreas. [Nat Rev Gastroenterol Hepatol] Abstract

Signal Transduction via TRPM3 Channels in Pancreatic β-Cells
The view that transient receptor potential melastatin-3 (TRPM3) represents an ionotropic steroid receptor of pancreatic β-cells linking insulin release with steroid hormone signaling is discussed. [J Mol Endocrinol] Abstract

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

INDUSTRY NEWS

Calibr and JDRF Partner to Support Diabetes Translational Research
The California Institute for Biomedical Research (Calibr) and JDRF announced a partnership to apply Calibr’s drug discovery expertise to type 1 diabetes research projects in collaboration with academic investigators from JDRF’s network. [PR Newswire Association LLC] Press Release

Boehringer Ingelheim and Eli Lilly and Company Submit New Drug Application to FDA for Empagliflozin, an Investigational Type 2 Diabetes Treatment
Boehringer Ingelheim and Eli Lilly and Company announced that a New Drug Application for the investigational sodium glucose co-transporter-2 inhibitor empagliflozin was recently submitted to the Food and Drug Administration (FDA) in the United States for the treatment of type 2 diabetes mellitus in adults. [Eli Lilly and Company] Press Release

£1 Million Awarded for New UK Research into Pancreatic Cancer
Six exciting new research projects totaling just under £1 million have been awarded grants by the Pancreatic Cancer Research Fund – thanks to the tireless fundraising of the charity’s supporters across the UK. [Pancreatic Cancer Research Fund] 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 14th World Congress of the International Pancreas and Islet Transplant Association (IPITA) 2013
September 24-27, 2013
Monterey, California

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

JOB OPPORTUNITIES

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

Postdoctoral Position – Pancreas Development (INSERM)

Postdoctoral Position – Mechano-Signaling in the Regulation of Pancreatic Cancer Progression (Fox Chase Cancer Center)

PhD Position (University Hospital Wuerzburg)

Postdoctoral Fellowship – Developmental Biology/Biophysics (University of Copenhagen)

Scientist/Specialist – Mitochondrial Function (The Nestlé Institute of Health Sciences)

Research Associate (Imperial College London – Faculty of Medicine)


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