Pancreatic Cell News Volume 9.49 | Dec 11 2018

TOP STORY

GSK3 Suppression Upregulates β-Catenin and c-Myc to Abrogate KRas-Dependent Tumors

Researchers showed that glycogen synthase kinase 3 (GSK3) was required for the in vitro and in vivo growth and survival of human mutant KRas-dependent tumors but was dispensable for mutant KRas-independent tumors. Further, inhibiting phosphorylation of GSK3 substrates c-Myc and β-catenin and their subsequent upregulation contributed to the antitumor activity of GSK3 inhibition. [Nat Commun] Full Article | Press Release

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Global Tudor-SN Transgenic Mice Are Protected from Obesity-Induced Hepatic Steatosis and Insulin Resistance

Scientists explored the impact of Tudor-staphylococcal nuclease (SN) on obesity induced by a high-fat diet (HFD) in mice, because the functional involvement of Tudor-SN in lipid metabolism in vivo was unknown. HFD-transgenic mice exhibited reductions in hepatic steatosis and systemic insulin resistance. [FASEB J] Abstract

Differential Effects of Type 1 Diabetes Mellitus and Subsequent Osteoblastic β-Catenin Activation on Trabecular and Cortical Bone in a Mouse Model

Researchers investigated whether WNT/β-catenin signaling had different effects on trabecular and cortical bone in type 1 diabetes mellitus (T1DM). They first established a streptozotocin-induced T1DM mouse model and then constitutively activated β-catenin in osteoblasts in the setting of T1DM. [Exp Mol Med] Full Article

Bioluminescent Reporter Assay for Monitoring ER Stress in Human Beta Cells

Scientists designed and evaluated a stress-induced reporter in which induction of stress correlated with increased light emission. This Gaussia luciferase-based reporter system employed the unconventional cytoplasmic splicing of XBP1 to report endoplasmic reticulum (ER) stress in cells exposed to known ER-stress inducers. [Sci Rep] Full Article

Oleate Disrupts cAMP Signaling, Contributing to Potent Stimulation of Pancreatic β-Cell Autophagy

Investigators treated MIN6 cells and mouse islets for 8-48 hours with either palmitate or oleate, and then monitored autophagic flux, signaling pathways, lysosomal biology and phospholipid profiles. Compared to palmitate, oleate more effectively stimulated both autophagic flux and clearance of autophagosomes. [J Biol Chem] Abstract | Full Article

Cyclic AMP-Dependent Protein Kinase A and EPAC Mediate VIP and Secretin Stimulation of PAK4 and Activation of Na⁺, K⁺-ATPase in Pancreatic Acinar Cells

Researchers examined the ability of VIP and secretin, which stimulate cAMP generation in pancreatic acini, to stimulate p21-activated kinase (PAK)4 activation, the signaling cascades involved and its possible role in activating Na⁺,K⁺-ATPase. [Am J Physiol Gastrointest Liver Physiol] Abstract

Combined Effect of GABA and GLP-1 Receptor Agonist on Cytokine-Induced Apoptosis in Pancreatic β-Cell Lines and Isolated Human Islets

Cytokine-induced apoptosis was reduced by either gamma-aminobutyric acid (GABA) or exendin-4 alone. This was markedly improved by combining GABA and exendin-4, resulting in a reversal of apoptosis. Akt pathway signaling was notably increased by the combination. [J Diabetes] Abstract

Zinc-Chelating Small Molecules Preferentially Accumulate and Function within Pancreatic β Cells

Investigators determined that zinc-rich β cells and islets preferentially accumulated 6-methoxy-8-p-toluenesulfonamido-quinoline in a zinc-dependent manner compared with exocrine pancreas. [Cell Chem Biol] Abstract | Press Release | Graphical Abstract

PANCREATIC CANCER

An Antibody Designed to Improve Adoptive NK-Cell Therapy Inhibits Pancreatic Cancer Progression in a Murine Model

Scientists developed an antibody-based natural killer (NK) cell-homing protein, named NK cell-recruiting protein-conjugated antibody. The effect of this protein on infiltration of NK cells into primary and metastatic pancreatic cancer was evaluated in vitro and in murine pancreatic ductal adenocarcinoma models. [Cancer Immunol Res] Abstract

GPx1 Is Involved in the Induction of Protective Autophagy in Pancreatic Cancer Cells in Response to Glucose Deprivation

Investigators first monitored the effect of glucose deprivation on autophagy and on the expression of glutathione peroxidase-1 (GPx1) in pancreatic ductal adenocarcinoma (PDA) cells under a glucose-free environment. Glucose starvation induced progressive autophagy activation in PDA cells via the activation of ROS/AMPK signaling. [Cell Death Dis] Full Article

Alantolactone Sensitizes Human Pancreatic Cancer Cells to EGFR Inhibitors through the Inhibition of STAT3 Signaling

Researchers discovered that alantolactone, a natural sesquiterpene lactone, potently inhibited human pancreatic cancer cells and suppressed constitutively activated signal transducer and activator of transcription 3 (STAT3). In contrast, alantolactone had little effect on the epidermal growth factor receptor (EGFR) pathway. [Mol Carcinog] Abstract

Downregulation of Long Noncoding RNA SNHG1 Inhibits Cell Proliferation, Metastasis, and Invasion by Suppressing the Notch-1 Signaling Pathway in Pancreatic Cancer

A real-time quantitative PCR detection system (qPCR) was used to detect the expression of SNHG1 in pancreatic cancer (PC) cells. Then, the SNHG1 knockdown cell was constructed with si-SNHG1. AsPC-1 and PANC1 cells were used to analyze the ability of cell proliferation, invasion, and migration. [J Cell Biochem] Abstract

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Melatonin in Type 2 Diabetes Mellitus and Obesity

The authors discuss the effect of melatonin and its receptors on glucose homeostasis, obesity and type 2 diabetes mellitus. [Nat Rev Endocrinol] Abstract

Circadian Clocks and Insulin Resistance

Investigators review the physiological links between circadian clocks, glucose metabolism and insulin sensitivity, and present current evidence for a relationship between circadian disruption and insulin resistance. [Nat Rev Endocrinol] Full Article

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

Novo Taps E-Therapeutics for Diabetes Target Discovery Drive

Novo Nordisk has enlisted e-therapeutics to support target discovery efforts at its recently-opened research center in Oxford, U.K. The collaboration will see e-therapeutics apply its platform for finding synergistic target combinations to a specific area of Type 2 diabetes. [Novo Nordisk A/S (Questex LLC)] Press Release

BioLineRx Announces Initiation of Triple Combination Arm of Phase IIa COMBAT/KEYNOTE-202 Study in Pancreatic Cancer Under Immuno-Oncology Collaboration

BioLineRx Ltd. announced the initiation of the triple combination arm of the Phase IIa COMBAT/KEYNOTE-202 study in patients with metastatic pancreatic cancer under its immuno-oncology collaboration with Merck & Co., Inc. [BioLineRx Ltd.] Press Release

Lawsuit Alleges NIH, FDA Let Clinical Trial Sponsors Off the Hook

A former top official at the Food and Drug Administration (FDA) and a longtime science journalist are suing the agency and the National Institutes of Health (NIH), saying they let clinical trial sponsors off the hook for reporting nearly a decade’s worth of important scientific data. [STAT News] Editorial

South Africa’s Science Academy Urges Update to Nation’s Genetics Laws

South Africa needs to overhaul the laws and ethical guidelines that govern its genetics research, testing and databases, says its national science academy — especially given the country’s troubled history of race-based discrimination. [Nature News] Editorial

NEW AACR Annual Meeting 2019
March 29-April 3, 2019
Atlanta, Georgia, United States

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

NEW Professor – Diabetology (Universität Tübingen)

Research Technologist – Pancreatic Cell Research (STEMCELL Technologies Inc.)

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

Postdoctoral Fellowship – Pancreatic Beta-Cell Development (City of Hope)

Postdoctoral Research Associate – Pancreas Development (University of Illinois)

Postdoctoral Research Fellow – Organ on a Chip Microfluidic Platform Design (University of Oslo)

Computational Biologist – Translational Cancer Research (Technical University of Munich)

Research Lab Specialist – Cancer Biology (University of Southern California)

Postdoctoral Position – Pancreatic Cancer (University Hospitals)

PhD Positions – Cancer Biology (Technical University of Munich)

Bench Research Fellowship – Cardiovascular Disease (Brigham & Women’s Hospital – Harvard Medical School)

Postdoctoral Position – Lung and Pancreatic Cancers (University of California San Francisco)

Postdoctoral Position – Stem Cells and Diabetes (A*STAR)

Postdoctoral Fellow – Epithelial Carcinogenesis (Spanish National Cancer Research Centre)

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