Volume 6.47 | Dec 1

Pancreatic Cell News 6.47 December 1, 2015
Pancreatic Cell News
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SENP1-Mediated NEMO deSUMOylation in Adipocytes Limits Inflammatory Responses and Type-1 Diabetes Progression
Scientists showed that mice with a adipocyte-specific deletion of the SUMO-specific protease SENP1 gene develop symptoms of type-1 diabetes mellitus, including hyperglycaemia and glucose intolerance with mild insulin resistance. Peri-pancreatic adipocytes from SENP1-deficient mice exhibit heightened NF-κB activity and production of proinflammatory cytokines, which induce CCL5 expression in adjacent pancreatic islets and direct cytotoxic effects on pancreatic islets. [Nat Commun] Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)

CK2 Acts as a Potent Negative Regulator of Receptor-Mediated Insulin Release In Vitro and In Vivo
The potential physiological relevance of β-Cell M3 muscarinic receptors (M3Rs) phosphorylation (or of G protein-coupled receptors in general) by casein kinase 2 (CK2) remains unknown. The authors showed that CK2-dependent phosphorylation of β-cell M3Rs significantly impairs M3R-mediated increases in insulin release in vitro and in vivo. [Proc Natl Acad Sci USA] Abstract

O-Linked β-N-Acetylglucosamine (O-GlcNAc) Acts as a Glucose Sensor to Epigenetically Regulate the Insulin Gene in Pancreatic Beta Cells
Using directed pharmacological approaches in the mouse insulinoma-6 cell line, researchers demonstrated that elevating nuclear O-GlcNAc increases intracellular insulin levels and preserves glucose stimulated insulin secretion during chronic hyperglycemia. [J Biol Chem] Full Article

SPECT of Transplanted Islets of Langerhans by Dopamine 2 Receptor Targeting in a Rat Model
Since islets express dopamine 2 (D2) receptors, they could be visualized by targeting this receptor. Therefore, the D2 receptor antagonist based tracer [125/123I][IBZM] was selected to visualize transplanted islets in a rat model. [Mol Pharm] Abstract

GSK-3β Mediates Dexamethasone-Induced Pancreatic β Cell Apoptosis
The effect of dexamethasone treatment on rat pancreatic β-cell line (INS-1) apoptosis (determined by TUNEL and Flow Cytometry), generation of reactive oxidative stress, and the phosphorylation status of glycogen synthase kinase-3β (GSK-3β) was determined. The inhibitory effect of GSK-3β inhibitor-lithium chloride on dexamethasone-induced β-cell apoptosis was also evaluated. [Life Sci] Abstract


Regulation of Oncogenic KRAS Signaling via a Novel KRAS-Integrin-Linked Kinase-hnRNPA1 Regulatory Loop in Human Pancreatic Cancer Cells
On the basis their finding that knockdown of either KRAS or ILK has a reciprocal effect on the other’s expression, the authors hypothesized the presence of an ILK-KRAS regulatory loop that enables pancreatic cancer cells to regulate KRAS expression. [Oncogene] Abstract

Development of a Panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma
Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-Systematic Evolution of Ligands by EXponential enrichment (SELEX) targeting human pancreatic ductal adenocarcinoma. [Sci Rep] Full Article

Tumor-Selective Use of DNA Base Excision Repair Inhibition in Pancreatic Cancer Using the NQO1 Bioactivatable Drug, β-Lapachone
Targeting base excision repair (BER) alone has limited therapeutic potential for pancreatic or other cancers due to a general lack of tumor-selectivity. The authors present a treatment strategy that makes BER inhibition tumor-selective and NAD(P)H:Quinone Oxidoreductase 1-dependent for therapy of most solid neoplasms, particularly for pancreatic cancer. [Sci Rep] Full Article

Pivotal Role of the Chromatin Protein Nupr1 in Kras-Induced Senescence and Transformation
Nupr1 is a chromatin protein, which cooperates with KrasG12D to induce PanIN formation and pancreatic cancer development in mice, though the molecular mechanisms underlying this effect remain to be fully characterized. The authors report that Nupr1 acts as a gene modifier of the effect of KrasG12D-induced senescence by regulating Dnmt1 expression and consequently genome-wide levels of DNA methylation. [Sci Rep] Full Article

The P2X7 Receptor Regulates Cell Survival, Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells
The authors determined the expression (real time PCR and Western blot) and localization (immunofluorescence) of P2X7R in human pancreatic ductal adenocarcinoma cell lines and a “normal” human pancreatic duct epithelial cell line. The function of P2X7R in proliferation (BrdU assay), migration (wound assay) and invasion (Boyden chamber with matrigel) was characterized. [Mol Cancer] Full Article

Minnelide Effectively Eliminates CD133+ Side Population in Pancreatic Cancer
Results indicated that triptolide enhanced and enriched the “stemness” in pancreatic ductal adenocarcinoma cell lines at a low dose of 12.5 nM, but also resulted in the regression of tumors derived from these cells. [Mol Cancer] Full Article

Take the If out of Diff: Definitive Endoderm
The Promise of Gene Therapy for Pancreatic Cancer
The reviewers explore research currently ongoing in French laboratories aimed at defeating pancreatic adenocarcinoma using non-viral therapeutic gene delivery, targeted transgene expression or oncolytic virotherapy that recently or will soon bridge the gap between experimental models of cancer and clinical trials. [Hum Gene Ther] Abstract

Causative Factors for Formation of Toxic Islet Amyloid Polypeptide Oligomer in Type 2 Diabetes Mellitus
Recently, human islet amyloid polypeptide (h-IAPP) was proposed to be the main component responsible for the cytotoxic pancreatic amyloid deposits in patients with type 2 diabetes mellitus. Since the causative factors of IAPP (or amylin) oligomer aggregation are not fully understood, this review will discuss the various forms of h-IAPP aggregation. [Clin Interv Aging] Full Article

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
Adocia Announces Positive Phase Ib Results of BioChaperone® Combo in Patients with Type 2 Diabetes
Adocia announced positive topline results from a Phase Ib randomized double-blind crossover trial of BioChaperone Combo in 24 subjects with type 2 diabetes under euglycemic clamp. [Adocia] Press Release

Debiotech and ARTORG Initiate an Exclusive Collaboration on the NextGeneration Artificial Pancreas
Debiotech SA, the ARTORG Center for Biomedical Engineering Research of the University of Bern – and the Division of Endocrinology, Diabetes and Clinical Nutrition of the Bern University Hospital “Inselspital” announced the start of an exclusive collaboration to develop a novel generation artificial pancreas. [Debiotech SA] Press Release

Clinical Trial for Type 1 Diabetes Begins at JGH, MUHC
Investigators at Montreal’s Lady Davis Institute at the Jewish General Hospital (JGH) and McGill University Health Centre (MUHG) have announced the start of a landmark clinical study aimed at restoring normal insulin secretion in people with longstanding type 1 diabetes. The treatment combines INGAP Peptide (Exsulin™), which stimulates growth of the insulin secreting islets, and ustekinumab (Stelera™), a drug approved for the treatment of psoriasis. [McGill University] Press Release

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NEW Cell Culture 2016
February 2-4, 2016
London, United Kingdom

Visit our events page to see a complete list of events in the pancreatic cell community.
NEW Postdoctoral Researcher – Pancreatic β-cells (University of Southern Denmark)

NEW Postdoctoral Researcher – Regenerative Medicine (The University of Texas)

NEW Postdoctoral/PhD Researcher – Cancer Epigenetics (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

NEW PhD Researcher – Cancer Genomics (Center for Human Genetics at the University of Leuven)

PhD Studentship – Cancer Biology (University of Salzburg)

Postdoctoral Fellowship (German Cancer Research Center)

Investigator – Cancer Biology (Wake Forest Baptist School of Medicine)

Postdoctoral Scientist – Pancreatic Cancer (German Cancer Research Center)

Faculty Positions – Regenerative Medicine for Organ Regeneration or Transplantation (The University of Texas Medical School At Houston)

Postdoctoral Research Fellow – Stem Cell Research (The University of Texas Medical School At Houston)

Postdoctoral Position – Type 2 Diabetes and Islet Biology (Lund University)

Scientist – Preclinical Immunology (Kanyos Bio)

Senior Clinical Lecturer – Cancer & Inflammation (Queen Mary University of London)

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