Pancreatic Cell News Volume 5.04 | Feb 4 2014

Grg3/TLE3 and Grg1/TLE1 Induce Monohormonal Pancreatic β Cells while Repressing α Cell Functions
Investigators showed that the Groucho corepressor protein 3 (Grg3) is expressed in almost all β cells throughout embryogenesis to adulthood. However, Grg3 is expressed in fewer nascent α cells and is progressively lost from α cells as endocrine cells mature into adulthood. [Diabetes] Abstract

A Humanized Mouse Model of Autoimmune Insulitis
Data showed that injection of small numbers of autoantigen-reactive CD4⁺ T cells can cause a targeted, destructive infiltration of pancreatic β cells. [Diabetes] Abstract

Dyrk1a Haploinsufficiency Induces Diabetes in Mice through Decreased Pancreatic Beta Cell Mass
Investigators showed that DYRK1A is expressed in pancreatic islets and provided evidence that changes in Dyrk1a gene dosage in mice strongly modulate glycemia and circulating insulin levels. Specifically, Dyrk1a-haploinsufficient mice showed severe glucose intolerance, reduced beta cell mass and decreased beta cell proliferation. [Diabetologia] Abstract

Maternal Microchimerism: Increased in the Insulin Positive Compartment of Type 1 Diabetes Pancreas but Not in Infiltrating Immune Cells or Replicating Islet Cells
The authors defined the cellular phenotype of maternal microchimeric cells (MMc) in control and type 1 diabetes pancreas. In normal pancreas, MMc positive for endocrine, exocrine, duct and acinar markers were identified suggesting that these cells are derived from maternal progenitors. Increased frequencies of MMc were observed in type 1 diabetes pancreas with particular enrichment in the insulin positive fraction. [PLoS One] Full Article

miRNA-375 Promotes Beta Pancreatic Differentiation in Human Induced Pluripotent Stem (hiPS) Cells
Knowing that microRNAs (miRNAs) are key players in various stages of pancreatic development, the authors present a novel and cost-effective strategy in which over-expression of miR-375 promotes pancreatic differentiation in hiPSCs in the absence of any other stimulator. [Mol Biol Rep] Abstract

Role of Vesicular Nucleotide Transporter VNUT (SLC17A9) in Release of ATP from AR42J Cells and Mouse Pancreatic Acinar Cells
The authors established the role of the vesicular nucleotide transporter (VNUT), SLC17A9, in storage and release of ATP (adenosine triphosphate). Freshly prepared acini from mice and AR42J rat acinar cells were used in this study. [Purinergic Signal] Abstract

PANCREATIC CANCER

Fascin Is Regulated by Slug, Promotes Progression of Pancreatic Cancer in Mice, and Is Associated with Patient Outcome
Researchers used KRas^G12D p53^R172H Pdx1-Cre mice to investigate the effects of fascin deficiency on development of pancreatic intraepithelial neoplasia, pancreatic ductal adenocarcinoma, and metastasis.[Gastroenterology] Abstract

CD133 Facilitates Epithelial-Mesenchymal Transition through Interaction with the ERK Pathway in Pancreatic Cancer Metastasis
Researchers investigated the role of CD133 in pancreatic cancer metastasis and its potential regulatory network. They found that CD133⁺ human pancreatic cancer cells were prone to generating metastatic nodules in in vivo models using immunodeficient mice. [Mol Cancer] Abstract | Full Article

Snail Contributes to the Maintenance of Stem Cell-Like Phenotype Cells in Human Pancreatic Cancer
The expression of Snail and its contribution to cancer stem cell marker expression, invasiveness, self-renewal, clonogenicity, and tumorigenicity of pancreatic cancer cells were studied. [PLoS One] Full Article

Islets of Langerhans from Prohormone Convertase-2 Knockout Mice Show α-Cell Hyperplasia and Tumorigenesis with Elevated α-Cell Neogenesis
Researchers evaluated the influence of total glucagon withdrawal on islets of Langerhans using prohormone convertase-2 knockout mice, in which α-cell hyperplasia is present from a young age and persists throughout life, in order to understand whether or not sustained glucagon deficit would lead to islet tumorigenesis. [Int J Exp Pathol] Abstract | Full Article

MicroRNA-375 Targets PDK1 in Pancreatic Carcinoma and Suppresses Cell Growth through the Akt Signaling Pathway
The authors demonstrated that microRNA-375 is downregulated in pancreatic carcinoma (PC) tissues and PC cell lines. [Int J Mol Med] Abstract

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S100 Family Signaling Network and Related Proteins in Pancreatic Cancer
The authors summarize the role and significance of the S100 family signaling network and related proteins in pancreatic cancer. [Int J Mol Med] Abstract

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NIH, Industry and Non-Profits Join Forces to Speed Validation of Disease Targets
The National Institutes of Health (NIH), ten biopharmaceutical companies and several nonprofit organizations launched an unprecedented partnership to transform the current model for identifying and validating the most promising biological targets of disease for new diagnostics and drug development. [National Institutes of Health]
Press Release

American Diabetes Association, Lilly Announce New Scholars Program for 74th Annual Scientific Sessions
The American Diabetes Association and Eli Lilly and Company announced the creation of the American Diabetes Association Scholars Program. The program, made possible through $1.1 million in support from Lilly, will provide scholarships for up to 100 scholars from outside the United States to attend this year’s Scientific Sessions, the world’s largest scientific and medical conference focused on diabetes and its complications. [American Diabetes Association] Press Release

AstraZeneca Completes the Acquisition of Bristol-Myers Squibb Share of Global Diabetes Alliance
AstraZeneca announced that it completed the acquisition of the entirety of Bristol-Myers Squibb’s interests in the companies’ diabetes alliance. [AstraZeneca] Press Release

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NEW Scientist Specialist – Diabetes/Metabolic Health (The Nestlé Institute of Health Sciences)

NEW Lab Technologist – Human Pluripotent Stem Cells (STEMCELL Technologies Inc.)

PhD Student – Beta-Cell ER Stress as Driver for Immune Activation in Early Type 1 Diabetes (KU Leuven)

Postdoctoral Research Scientist – Imaging GTPase Activation in Cancer (Cancer Research UK Beatson Institute in Glasgow)

Postdoctoral Research Scientist – RAC and RAL Signaling Downstream of KRAS Mutation in Pancreatic and Colon Cancer (Cancer Research UK Beatson Institute in Glasgow)

Postdoctoral Fellowship Position – Mechanisms of Action in Obesity and Diabetes Pathogenesis (NIH/NIDDK)

Postdoctoral Fellow – Morphogenetic Signaling Pathways in Development and Disease (University of Rochester Medical Center)

PhD Student Position – Diabetes and Bone Regeneration (KU Leuven)

Postdoctoral Position – Development of Cellular Assays for Drug Development and Testing in Diabetes Treatment (Université de Sherbrooke)

Postdoctoral Position – Pancreatic Cancer Research (University of Texas Health Science Center at San Antonio)

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