Pancreatic Cell News Volume 10.29 | Jul 30 2019

TOP STORY

Oncogenic KRAS Reduces Expression of FGF21 in Acinar Cells to Promote Pancreatic Tumorigenesis in Mice on a High-Fat Diet

Researchers performed immunohistochemical analyses of fibroblast growth factor 21 (FGF21) levels in human pancreatic tissue arrays, comprising 59 pancreatic ductal adenocarcinoma specimens and 45 non-tumor tissues. They also studied mice with tamoxifen-inducible expression of oncogenic KRAS in acinar cells and fElas^CreERT mice. Kras^G12D/+ mice were placed on a high fat diet or regular chow diet and given injections of rhFGF21 or vehicle. [Gastroenterology] Abstract

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DIABETES & PANCREATITIS

Lysosomal Degradation of Newly Formed Insulin Granules Contributes to β Cell Failure in Diabetes

Researchers report that metabolic stress markedly enhances macroautophagy-independent lysosomal degradation of nascent insulin granules. In different model systems of diabetes including of human origin, stress-induced nascent granule degradation contributed to loss of insulin along with mammalian/mechanistic Target of Rapamycin-dependent suppression of macroautophagy. [Nat Commun] Full Article

Dracorhodin Perchlorate Protects Pancreatic β-Cells against Glucotoxicity- or Lipotoxicity-Induced Dysfunction and Apoptosis In Vitro and In Vivo

Investigators established a Pdx1 promoter-dependent luciferase system and identified the natural compound dracorhodin perchlorate (DP) as an effective promotor of Pdx1 expression. They further demonstrated that DP could significantly inhibit β-cell apoptosis induced by 33 mM glucose or 200 μM palmitate by interfering with endoplasmic reticulum stress and mitochondrial pathways and enhance insulin secretion as well. [FEBS J] Abstract

In Vitro and In Vivo Effects of Insulin-Producing Cells Generated by Xeno-Antigen Free 3D Culture with RCP Piece

Scientists established a 3D culture using a human recombinant peptide (RCP) petaloid μ-piece with xeno-antigen free reagents. Briefly, they employed our two-step protocol to differentiate adipose-derived stem cells in 96-well dishes and cultured cells in xeno-antigen free reagents with 0.1 mg/mL RCP μ-piece for seven days, followed by addition of histone deacetylase inhibitor for 14 days. [Sci Rep] Full Article

m⁶A mRNA Methylation Regulates Human β-Cell Biology in Physiological States and in Type 2 Diabetes

Investigators report that the m⁶A landscape segregated human type 2 diabetes (T2D) islets from controls significantly better than the transcriptome and that m⁶A was vital for β-cell biology. m⁶A sequencing in human T2D islets revealed several hypomethylated transcripts that were involved in cell-cycle progression, insulin secretion, and the insulin/IGF1–AKT–PDX1 pathway. [Nat Metab] Abstract

Connexin 43 Functions as a Positive Regulator of Stem Cell Differentiation into Definitive Endoderm and Pancreatic Progenitors

Scientists identified the expression pattern of connexin 43, a gap junction channel protein, in human embryonic stem cell-derived definitive endoderm and primitive gut tube cells, representing early lineages for posterior foregut, pancreatic progenitors, pancreatic endocrine progenitors and islet cells. [iScience] Abstract | Graphical Abstract | Full Article

Coxsackievirus B Persistence Modifies the Proteome and the Secretome of Pancreatic Ductal Cells

Researchers established persistent group B Coxsackieviruses (CVVB) infections in a human pancreatic ductal-like cell line PANC-1 using two distinct CVB1 strains, and profiled infection-induced changes in cellular protein expression and secretion using mass spectrometry-based proteomics. [iScience] Abstract | Graphical Abstract | Full Article

PANCREATIC CANCER

YAP1-Mediated Pancreatic Stellate Cell Activation Inhibits Pancreatic Cancer Cell Proliferation

Investigators determined that Yes-associated protein 1 (YAP1) was highly expressed in the nuclei of pancreatic ductal adenocarcinoma-derived activated pancreatic stellate cells (PSCs). RNAi-mediated or pharmacological inhibition of YAP1 led to PSC deactivation. [Cancer Lett] Abstract

β8 Integrin Mediates Pancreatic Cancer Cell Radiochemoresistance

The authors identified β8 integrin in a high-throughput knockdown screen in three-dimensional, extracellular matrix-based cell cultures for novel focal adhesion protein targets as critical determinant of pancreatic ductal adenocarcinoma (PADC) cell radiochemoresistance. Intriguingly, β8 integrin localized with the golgi apparatus perinuclearly in PDAC cells and resection specimen from PDAC patients. [Mol Cancer Res] Abstract

Enhanced Morphological and Functional Differences of Pancreatic Cancer with Epithelial or Mesenchymal Characteristics in 3D Culture

In 3D culture, PK-1 cells had high E-cadherin and low vimentin expression and exhibited a round-like appearance encircled by flat cells. PANC-1 cells had high vimentin and low E-cadherin expression and formed grape-like spheres. [Sci Rep] Full Article

Cadmium Exposure Induces Pancreatic β-Cell Death via a Ca²⁺-Triggered JNK/CHOP-Related Apoptotic Signaling Pathway

The authors found that cadmium (Cd) exposure significantly inhibited insulin secretion and cell viability in the pancreatic β-cell-derived RIN-m5F cells. Cd exposure induced apoptotic events, including the increased populations of apoptotic cells and sub-G1-hypodiploid cells, and caspase-3/-7/-9 and poly (ADP-ribose) polymerase activation, which largely depended on the activation of c-Jun N-terminal kinase and C/EBP homologous protein. [Toxicology] Abstract | Graphical Abstract

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Rethinking the Role of the Brain in Glucose Homeostasis and Diabetes Pathogenesis

The brain plays a major role in homeostatic processes ranging from control of body temperature and fat mass to blood pressure and volume. Tight regulation of the circulating glucose level is similarly crucial for survival, and since the brain relies almost exclusively on glucose as a fuel source, it seems counterintuitive to think that the brain does not also play an important role in glucose homeostasis. [J Clin Invest] Full Article

Omics Approaches in Pancreatic Adenocarcinoma

Pancreatic cancer is expected to become the second leading cause of cancer-related death by 2030. Therefore, advances in screening, prevention and treatment are urgently needed. Fortunately, a wide range of approaches could help shed light in this area. [Cancers] Full Article

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

TYME Technologies Announces New Collaboration with NYU Langone to Advance TYME’s Cancer Metabolism-Based Therapy, SM-88

Tyme Technologies, Inc. announced a new research collaboration with NYU Langone Health to advance the development of innovative treatments for patients with metastatic cancers, including pancreatic cancer. The collaboration will leverage NYU Langone’s state-of-the-art technologies to help inform the development of clinical therapies, focusing on identifying potential future biomarkers or combination approaches to treat cancer. [TYME Technologies] Press Release

Lexicon Pharmaceuticals Provides Preliminary Update for Zynquista™ (Sotagliflozin) Type 2 Diabetes Phase III Program

Lexicon Pharmaceuticals, Inc. received preliminary topline results from Sanofi for three Phase III trials of Zynquista™ in adults living with type 2 diabetes from the InSynchrony clinical program. Lexicon has not yet received the underlying data, and expects to conduct its own review and validation and statistical analysis of the data when they are received. [Lexicon Pharmaceuticals, Inc.] Press Release

Crinetics Pharmaceuticals to Receive Final Award of SBIR Grant from NIH for Congenital Hyperinsulinism

Crinetics Pharmaceuticals, Inc. announced that it would receive up to approximately $0.9 million in continued funding under its Small Business Innovation Research grant from the National Institute of Diabetes and Digestive and Kidney diseases of the National Institutes of Health. [Crinetics Pharmaceuticals, Inc.] Press Release

Medical Journal Editors Expect Authors to Disclose Conflicts of Interest- But Don’t Disclose Their Own

Virtually all top medical journals require authors to disclose potential conflicts of interest, but few- just 12%- apply that same medicine to their own editors by publicly disclosing editors’ financial ties to industry, a study has found. [ScienceMagazine] Editorial

Cuts and Dismissive Remarks Unnerve Mexican Scientists

The initially warm relations between Mexico’s academic community and the country’s new president, Andrés Manuel López Obrador, have decidedly cooled. A package of harsh austerity measures, implemented on 3 May, has had a deep impact on federally funded laboratories and institutes; it includes a 30% cut to fuel for vehicles and office supplies and a 50% cut to international travel funds and payments to contract workers. Scientists say the cuts are a serious threat to the future of Mexican research. [ScienceMagazine] Editorial

UK Prime Minister Boris Johnson’s Hardline Brexit Stance Stokes Fears for Scientists

Boris Johnson, a charismatic and incautious politician with scant public views on science, became U.K. prime minister last week. He immediately packed his Cabinet with ministers pledging to exit the European Union by a 31 October deadline, even without a deal in place for an amicable divorce—the “no-deal Brexit” that economists predict would cause a recession and scientists say would cause additional hardships for research. [ScienceMagazine] Editorial

NEW Victorian Comprehensive Cancer Centre (VCCC) Research Conference 2019
September 16-17, 2019
Victoria, Australia

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

NEW Scientific Communications Coordinator (STEMCELL Technologies Inc.)

NEW Postdoctoral Researcher – Type 1 Diabetes Pathogenesis (Karolinska Institutet)

Research Associate – Pathology and Treatment of Diabetes (King’s College London)

Postdoctoral Fellowship – Jak-Stat Signaling in Prostate/Pancreatic Cancer (Medical College of Wisconsin)

Research Scientist – Endocrine Pancreas Development (Helmholtz Zentrum München)

Postdoctoral Position – Immunology (Roswell Park Cancer Institute)

Postdoctoral Researcher – Pancreas Cancer Research (Fred Hutchinson Cancer Research Center)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Cancer Drug Response Research (University of Texas at Austin)

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

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

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

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