Pancreatic Cell News Volume 10.38 | Oct 1 2019

TOP STORY

Modeling Human Hepato-Biliary-Pancreatic Organogenesis from the Foregut-Midgut Boundary

Researchers report the continuous patterning and dynamic morphogenesis of hepatic, biliary and pancreatic structures, invaginating from a three-dimensional culture of human pluripotent stem cells. The boundary interactions between anterior and posterior gut spheroids differentiated from human pluripotent stem cells enables retinoic acid-dependent emergence of hepato-biliary-pancreatic organ domains specified at the foregut-midgut boundary organoids in the absence of extrinsic factors. [Nature] Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Homozygous Receptors for Insulin and Not IGF-1 Accelerate Intimal Hyperplasia in Insulin Resistance and Diabetes

Investigators report that intima hyperplasia was attenuated in SMIRKO mice, but not in SMIGF1RKO mice. In vascular smooth muscule cells, deleting IGF1R increased homodimers of IR, enhanced insulin binding, stimulated p-Akt and proliferation, but deleting IR decreased responses to insulin and IGF-1. [Nat Commun] Full Article

Essential Role of Glucokinase in the Protection of Pancreatic β Cells to the Glucose Energetic Status

Upon glucose decline caused by stimulation with either 2-deoxyglucose or metformin, only pancreatic β cells showed an increase in cell death. When researchers transfected either mouse insulinoma cell or human embryo kidney cells with a phospho-mutant form of B cell lymphoma 2 associated agonist of cell death at serine 155, an increase in the pro-survival factor B cell lymphoma 2 was detected in pancreatic β cells and not in human embryonic kidney cells in the presence of energetic stressors. [Cell Death Discov] Full Article

Orphan G-Protein Coupled Receptor 183 (GPR183) Potentiates Insulin Secretion and Prevents Glucotoxicity-Induced β-Cell Dysfunction

Microarray expression indicated that 36 orphan GPCRs were restricted in human islets, while 55 receptors overlapped between human islets and INS-1 cells. GPR183 showed higher expression in diabetic compared to non-diabetic human islets. GPR183 expression co-localized with β-cells while it was lacking in α-cells in human islets. [Mol Cell Endocrinol] Full Article

Human Antigen Leucocyte (HLA)-G and HLA-E Are Differentially Expressed in Pancreatic Disorders

Human Leukocyte Antigen (HLA)-G and -E expression was evaluated by immunohistochemistry in three different areas. Acini and islets from histologically normal pancreas specimens exhibited higher HLA-G and -E expression compared to corresponding areas from all other patient groups. [Hum Immunol] Abstract

Regulation of CFTR Bicarbonate Channel Activity by WNK1: Implications for Pancreatitis and CFTR-Related Disorders

Scientists examined the mechanisms of the cystic fibrosis transmembrane conductance regulator (CFTR) HCO₃⁻ channel regulation by [Cl^–]i-sensitive kinases using an integrated electrophysiological, molecular, and computational approach including whole-cell, outside-out, and inside-out patch clamp recordings and molecular dissection of WNK1 and CFTR proteins. They analyzed the effects of pancreatitis-causing CFTR mutations on the WNK1-mediated regulation of CFTR. [Cell Mol Gastroenterol Hepatol] Abstract | Full Article | Graphical Abstract

PANCREATIC CANCER

Dedifferentiation Process Driven by Radiotherapy-Induced HMGB1/TLR2/YAP/HIF-1α Signaling Enhances Pancreatic Cancer Stemness

The authors confirmed that X-ray irradiation induced differentiation of CD133^– pancreatic cancer cells, from either sorted from patient samples or established cell lines, into cancer stem-like cells. Using an in vitro co-culture model, X-ray irradiation induced dying cells to release HMGB1, which further promoted CD133^– pancreatic cancer cells regaining stem cell traits, such as higher sphere forming ability and expressed higher level of stemness-related genes and proteins. [Cell Death Dis] Full Article

Modulating TAK1 Expression Inhibits YAP and TAZ Oncogenic Functions in Pancreatic Cancer

Differentially expressed transcripts between pancreatic cancer cells expressing scramble or TGFβ-activated kinase 1 (TAK1)-specific shRNA were annotated for functional interrelatedness by Ingenuity Pathway Analysis. TAK1 expression was modulated by using different GSK3 inhibitors, including LY2090314. [Mol Cancer Ther] Abstract | Full Article

A GLIS3-CD133-WNT Signaling Axis Regulates the Self-Renewal of Adult Murine Pancreatic Progenitor-Like Cells in Colonies and Organoids

Using an ex vivo colony/organoid culture system, investigators demonstrated that stem/progenitor-like cells had self-renewal and multilineage differentiation potential. They named these cells pancreatic colony-forming units because they could give rise to three-dimensional colonies. [J Biol Chem] Abstract | Full Article

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Glucagon-Like Peptide 1 (GLP-1)

Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. The authors provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases. [Mol Metab] Full Article

NF-κB Dependent Chemokine Signaling in Pancreatic Cancer

NF-κB regulates the expression of chemokines and their receptors that mediate autocrine and paracrine loops among tumor cells but also cross-signaling between tumor cells and the stroma. Investigators focus on NF-κB-mediated chemokine signaling, with an emphasis on therapy resistance in pancreatic cancer. [Cancers] Full Article

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University of Utah Biomedical Engineer Receives $1.5 Million Grant to Develop Innovative Methods to Halt Spread of Cancer

University of Utah biomedical engineering assistant professor Tara Deans has received this year’s National Institutes of Health Director’s New Innovator Award and a $1.5 million grant to develop a method that could help stop the spread of cancer by using specially engineered blood platelets to seek and destroy tumor cells in the bloodstream.” [The University of Utah] Press Release

Cedars-Sinai Awarded $10 Million to Study Pancreatic Diseases

A scientific team led by Cedars-Sinai has been awarded $10 million from the US Department of Defense to investigate the risk factors and behaviors that contribute to pancreatic diseases and develop potential treatments and lifestyle recommendations to prevent them. [Cedars-Sinai] Press Release

India Pushes for Alternatives to Animals in Biomedical Research

India has become the latest nation to explore using emerging technologies such as organs-on-a-chip to replace animals in research. Earlier this month, the national regulator for biomedical research recommended fast-tracking investments in technologies that can replace animals. [Nature News] Editorial

China: How Science Made a Superpower

The opening ceremony of the 2008 Olympic Games in Beijing featured ancient China’s four great inventions: the compass, printing press, paper and gunpowder. The lesson on display, as taught in classrooms across the country that today publishes the most research papers, is that Chinese innovation in science and technology changed the world. [Nature News] Editorial

Two-Thirds of Researchers Report ‘Pressure to Cite’ in Nature Poll

An online poll answered by more than 4,300 Nature readers suggests that most researchers have felt pressured by peer reviewers to cite studies in their papers that seem unnecessary. [Nature News] Editorial

NEW Molecular Mechanisms of Electrical Signaling in Health and Disease
July 12-17, 2020
South Hadley, Massacheussetts, United States

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NEW Research Assistant – Pancreatic Adenocarcinoma Spheroids (The University of Osnabrück)

Group Leader – Diabetes Research (International Centre for Genetic Engineering and Biotechnology)

Faculty Position – Cancer Biology (Children’s Research Institute at UT Southwestern)

Postdoctoral Fellow – Pancreatic Cancer (The University of Alabama at Birmingham)

Postdoctoral Position – Pancreatic Ductal Adenocarcinoma (IT University of Copenhagen)

Lab Aide – Pancreatic Cancer Research (Fred Hutchinson Cancer Research Center)

Research Technition – Diabetes, Allergies, and Lung Diseases (Helmholtz Zentrum München)

Postdoctoral Researcher – Auto-Immunity (Benaroya Research Institute)

Postdoctoral Researcher – Endocrinology, Diabetes, and Metabolism (The University of Alabama at Birmingham)

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

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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