Pancreatic Cell News Volume 10.10 | Mar 19 2019

TOP STORY

Phosphoproteomics Reveals the GSK3-PDX1 Axis as a Key Pathogenic Signaling Node in Diabetic Islets

Deep phosphoproteomic analysis of human islets chronically treated with high glucose demonstrated a conserved glucotoxicity-dependent role of GSK3 kinase in regulating insulin secretion. The ability of beta cells to secrete insulin in response to glucose was rescued almost completely by pharmacological inhibition of GSK3. [Cell Metab] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate

Researchers identified a p120ctn-regulated mechanism for coordination of organ architecture and cellular fate mediated by differential E-cadherin based cell sorting. Reduced p120ctn expression was necessary and sufficient to re-localize a subset of progenitors to the peripheral tip domain, where they acquired an acinar fate. [Dev Cell] Full Article | Press Release | Graphical Abstract

Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans

Islets of nondiabetic mice and humans showed a substantial overlap of upregulated cilia genes that were linked to cell-cycle progression. The shRNA-mediated suppression of KIF3A, essential for ciliogenesis, impaired division of MIN6 beta cells as well as in dispersed primary mouse and human islet cells, as shown by decreased BrdU incorporation. [Cell Rep] Abstract | Graphical Abstract

Single-Cell Heterogeneity Analysis and CRISPR Screen Identify Key β-Cell-Specific Disease Genes

Scientists mapped both β-cell-specific genes and disease signature genes to the insulin regulatory network identified from a genome-wide CRISPR screen. Their integrative analysis discovered the previously unrecognized roles of the cohesin loading complex and the NuA4/Tip60 histone acetyltransferase complex in regulating insulin transcription and release. [Cell Rep] Abstract | Graphical Abstract

The E3 Ubiquitin Ligase Parkin Is Dispensable for Metabolic Homeostasis in Murine Pancreatic β Cells and Adipocytes

Researchers observed that insulin secretion, β-cell formation, and islet architecture were preserved in parkin-deficient β cells and islets, suggesting that parkin was not necessary for control of β-cell function and islet compensation for diet-induced obesity. Although transient parkin deficiency mildly impaired mitochondrial turnover in β-cell lines, parkin deletion in primary β cells yielded no deficits in mitochondrial clearance. [J Biol Chem] Abstract | Full Article

Offspring of Mice Exposed to a Low-Protein Diet in Utero Demonstrate Changes in mTOR Signaling in Pancreatic Islets of Langerhans, Associated with Altered Glucagon and Insulin Expression and a Lower β-Cell Mass

mRNA levels for mammalian target of rapamycin (mTOR) control complex genes mTOR, Rictor and Raptor were elevated at seven days in low-protein mice, as were the mTOR and Raptor proteins. Proglucagon gene expression was similarly increased, but not insulin or the immune/metabolic defense protein STING. [Nutrients] Full Article | Graphical Abstract

Silenced CHOP Protects Pancreatic B-Cell Function by Targeting Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α through Nuclear Factor-κB Signaling Pathway in Diabetes Mellitus

Scientists showed that high glucose (HG) increased C/EBP homologous protein (CHOP) and inhibited peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression and ameliorated apoptosis in pancreatic β cells. Silenced CHOP elevated PGC-1α expression and ameliorated HG-induced apoptosis in pancreatic β cells. [J Cell Biochem] Abstract

PANCREATIC CANCER

An Auristatin-Based Antibody-Drug Conjugate Targeting HER3 Enhances the Radiation Response in Pancreatic Cancer

Investigators found that the monomethylauristatin E-based HER3 antibody-drug conjugate was efficiently internalized in tumor cells, increased the fraction of cells arrested in G2/M, which is the most radiosensitive phase of the cell cycle, and promoted programmed cell death of irradiated HER3-positive pancreatic cancer cells. [Int J Cancer] Abstract

Plasma-Activated Medium Triggers Cell Death and the Presentation of Immune Activating Danger Signals in Melanoma and Pancreatic Cancer Cells

A sealed dielectric-barrier discharge was used to disentangle the effect of reactive nitrogen species from that of reactive oxygen species on cancer cells. Two cancers characterized by poor prognosis were investigated: metastatic melanoma and pancreatic cancer. [Sci Rep] Full Article

Sensitization and Synergistic Anti-Cancer Effects of Furanodiene Identified in Zebrafish Models

The authors successfully established zebrafish xenografts with five various human cancer cell lines and validated these models with anti-cancer drugs used clinically for treating human cancer patients. They found that Furanodiene was therapeutically effective for human JF 305 pancreatic cancer cells and MCF-7 breast cancer cells xenotranplanted into zebrafish. [Sci Rep] Full Article

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Current Understanding of the Role of Gut Dysbiosis in Type 1 Diabetes

The authors discuss recent advancements depicting the role of intestinal dysbiosis on immunity and autoimmunity in type 1 diabetes (T1D). They also discuss therapies aimed at maintaining a healthy gut barrier as prevention strategies for T1D. [J Diabetes] Abstract

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AzurRx BioPharma Announces Presentation on Its Positive Phase II Data in MS1819-SD in Chronic Pancreatitis

AzurRx BioPharma, Inc. announced that a presentation entitled “Results from a Phase II Study of MS1819, a Recombinant Lipase for the Treatment of Exocrine Pancreatic Insufficiency in Patients with Chronic Pancreatitis” authored by Dr. Nam Q. Nguyen, et al., will be delivered by Dr. Nguyen. [Press release from AzurRx BioPharma, Inc. discussing research to be presented at the 2019 Digestive Disease Week (DDW) Conference, San Diego] Press Release

Hemispherx Biopharma Announces Significant Progress in its Ampligen Pancreatic Cancer Program and Multiple Ampligen+Checkpoint Blockade Immuno-Oncology Programs

Hemispherx Biopharma Inc. announced the first of a series of planned quarterly press release updates highlighting the progress and achievement of milestones in the company’s ongoing clinical trials evaluating Ampligen’s ability to reprogram tumor microenvironments and increase the effectiveness of existing cancer immunotherapy, such as checkpoint blockade therapies. [Hemispherx Biopharma, Inc.] Press Release

Lian Receives ENGINE Grant for Stem Cell-Based Diabetes Therapy

Xiaojun Lian, assistant professor of biomedical engineering, was one of three recipients of the Pennsylvania State University College of Engineering’s Engineering for Innovation & Entrepreneurship (ENGINE) grant for his project titled “Small Molecule-Based Definitive Endoderm Kit and Pancreatic Progenitor Kit for Stem Cell Research and Therapy.” The project focuses on differentiating stem cells into pancreatic beta cells to be used for therapies to treat Type 1 diabetes. [Pennsylvania State University] Press Release

Trump Proposes Slashing Science Spending at the NSF

US President Donald Trump has proposed cuts across the board at the National Science Foundation (NSF) in his 2020 budget request to Congress. The biggest decreases would hit funding for research in Antarctica and the Arctic, the geosciences, maths and physical sciences. [Nature News] Editorial

Survey Highlights “Shocking” Gender Bias Among PI Pay in UK

Organizers of a survey of early-career scientists in the UK say they are shocked by the picture it paints of gender bias in British science. Women principal investigators (PIs) who have started their own lab in recent years are paid thousands of pounds a year less than men at the same stage of their career, the results show. [The Scientist] Editorial

NEW Advanced Cell Therapies and Tissue Engineering
November 14-16, 2019
Milan, Italy

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NEW Postdoctoral Fellowship – Regenerative Medicine and Metabolic Biology (Indiana Biosciences Research Institute)

NEW Research Positions – Pancreatic Beta-Cells (Université de Montréal)

Postdoctoral Fellowship – Pancreatic Islet Cells (Karolinska Institutet)

Postdoctoral Position – Diabetes (University of Minnesota)

Postdoctoral Fellow – Pancreatic Development & Islet Biology (Vanderbilt University)

Junior Scientists – Diabetes (Lund University)

Postdoctoral Position – Pancreatic Tissue Engineering (King’s College London)

Postdoctoral Research Assistant – Stem Cell and Cancer Research (University of Oxford)

Professor – Diabetes (University of California, San Diego)

Postdoctoral Fellowship – Pancreatic Cancer (Dartmouth College)

Postdoctoral Fellow – Neuroscience and Diabetes (The Child Health Institute of New Jersey)

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