Pancreatic Cell News Volume 6.49 | Dec 15 2015

Type I Interferons Mediate Pancreatic Toxicities of PERK Inhibition
Scientists demonstrated that activation of type 1 interferon signaling occurs upon pancreatic endoplasmic reticulum kinase (PERK) ablation and is responsible for pancreatic injury and the loss of exocrine and endocrine tissues and functions. [Proc Natl Acad Sci USA] Abstract

Disruption of O-Linked N-Acetylglucosamine Signaling Induces ER Stress and β Cell Failure
The requirement of O-GlcNAcylation for maintaining glucose homeostasis by regulating pancreatic β cell mass and function is unclear. The authors revealed that mice lacking β cell O-linked N-acetylglucosamine transferase developed diabetes and β cell failure. [Cell Rep] Full Article | Graphical Abstract

Monitoring C-Peptide Storage and Secretion in Islet Beta Cells In Vitro and In Vivo
In vivo fluorescence imaging of the pancreatic surface allows visual assessment of pancreatic islet insulin content, and the authors demonstrated that C-peptide bearing superfolder green fluorescent protein visibly declines upon diabetes progression in live lepR^db/db mice. [Diabetes] Abstract

A Functional Circadian Clock Is Required for Proper Insulin Secretion by Human Pancreatic Islet Cells
Scientists aimed at unravelling the impact of a functional human islet clock on insulin secretion and gene transcription. Circadian clock disruption resulted in a significant decrease of both acute and chronic glucose-stimulated insulin secretion. [Diabetes Obes Metab] Abstract

Npas4 Transcription Factor Expression Is Regulated by Calcium Signaling Pathways and Prevents Tacrolimus-Induced Cytotoxicity in Pancreatic Beta Cells
Researchers examined the calcium-induced expression of the cytoprotective beta cell transcription factor Npas4. Pharmacological inhibition implicated the calcineurin, Akt/protein kinase B and Ca²⁺/calmodulin-dependent protein kinase signaling pathways in the regulation of Npas4 transcription and translation. [J Biol Chem] Abstract | Full Article

A Dual Proteomic Approach Identifies Regulated Islet Proteins during Beta Cell Mass Expansion in Vivo
The aim of this study was to characterize pregnancy-induced changes in the islet proteome at the peak of beta cell proliferation in mice. Islets from pregnant and non-pregnant littermates were compared via two proteomic strategies. [Mol Endocrinol] Abstract | Full Article

Transplantation of Mesenchymal Stem Cells Improves Type 1 Diabetes Mellitus
Scientists showed that the intrapancreatic transplantation of mesenchymal stem cells elevates serum insulin and C-peptide, while decreasing blood glucose. [Cell Tissue Res] Abstract

Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats with Acute and Chronic Pancreatitis
Researchers investigated the effect of rat fetal membrane-derived mesenchymal stem cells and human amnion-derived mesenchymal stem cells on the inflammatory reaction in vitro and therapeutic effects in rats with acute and chronic pancreatitis. [Pancreas] Abstract

PANCREATIC CANCER

Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer
Researchers demonstrated the role of previously identified familial pancreatic cancer susceptibility genes such as BRCA2, CDKN2A and ATM, and identified novel candidate genes harboring rare, deleterious germline variants for further characterization. [Cancer Discov] Abstract | Full Article

MYB Is a Novel Regulator of Pancreatic Tumor Growth and Metastasis
MYB was aberrantly expressed in all malignant cases of pancreas, whereas it remained undetectable in normal pancreas. [Br J Cancer] Abstract

Low Intratumoral Regulatory T Cells and High Peritumoral CD8⁺ T Cells Relate to Long-Term Survival in Patients with Pancreatic Ductal Adenocarcinoma after Pancreatectomy
Using immunohistochemistry, the authors explored the clinical significance of intratumoral or peritumoral CD4⁺Foxp3⁺ regulatory T cells and CD8⁺ T cells in the tumor microenvironment and analyzed their relation to the prognosis of pancreatic ductal adenocarcinoma in a consecutive series of ninety two patients after resection. [Cancer Immunol Immunother] Abstract

Activation of Pancreatic Stellate Cells Involves an EMT-Like Process
The authors examined whether the epithelial-mesenchymal transition (EMT) process might play a role in pancreatic stellate cells (PSC) activation. PSCs were isolated from a rat pancreas and characterized using immunofluorescence and immunocytochemistry. [Int J Oncol] Abstract

Pathobiology of Pancreatic Cancer: Implications on Therapy
With the identification of inter- and intratumoral genomic rearrangements and the detection of cancer stem cells through phenotypic variations of cancer cells there are increasing options for pancreatic cancer therapy. [Expert Rev Anticancer Ther] Abstract

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Novo Nordisk and IBM Partner to Build Diabetes Care Solutions on the Watson Health Cloud
Novo Nordisk A/S and IBM Watson Health announced that the two companies will work together to create diabetes solutions built on the Watson Health Cloud. [Novo Nordisk A/S] Press Release

Poxel Announces Imeglimin Phase IIb Initiation in Japan
Poxel SA provided an update on the clinical development of its two lead pipeline assets: Imeglimin, the first in a new class of oral anti-diabetic agents, and PXL770, a direct activator of the adenosine monophosphate-activated kinase. [Poxel SA] Press Release

Merck KGaA, Darmstadt, Germany, Decides Not to Pursue Evofosfamide Further in Soft Tissue Sarcoma and Pancreatic Cancer
Merck KGaA announced that it is not planning to file for approval of evofosfamide in advanced soft tissue sarcoma and advanced pancreatic adenocarcinoma. [Merck KGaA] Press Release

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NEW PhD Researcher – Signaling in Colorectal/Pancreatic Cancer (DKFZ)

NEW Post-Doc Researcher – Liver and Pancreas Development (Université Catholique de Louvain)

Clinical Research Fellow – Pancreatic Ductal Adenocarcinoma (Imperial College London)

Postdoctoral Researcher – Pancreatic Cancer Radioimaging (University of Oxford)

MD/PhD Researcher – Biomedical Sciences (Hannover Medical School)

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

PhD Studentship – Cancer Biology (University of Salzburg)

Postdoctoral Fellowship (German Cancer Research Center)

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

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

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