Pancreatic Cell News Volume 10.42 | Oct 29 2019

TOP STORY

N-WASP Control of LPAR1 Trafficking Establishes Response to Self-Generated LPA Gradients to Promote Pancreatic Cancer Cell Metastasis

Scientists showed that N-WASP drove pancreatic cancer metastasis, with roles in both chemotaxis and matrix remodeling. Lysophosphatidic acid, a signaling lipid abundant in blood and ascites fluid, was both a mitogen and chemoattractant for cancer cells. [Dev Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

RNA Binding Protein HuD Contributes to β-Cell Dysfunction by Impairing Mitochondria Dynamics

Researchers demonstrated that HuD played a novel role in the regulation of mitochondrial dynamics by promoting mitochondrial fusion. They showed enhanced mitochondrial fragmentation in the pancreas of db/db mice and HuD KO mice. [Cell Death Differ] Abstract

Atorvastatin Targets the Islet Mevalonate Pathway to Dysregulate mTOR Signaling and Reduce β-Cell Functional Mass

Supplementation of the mevalonate pathway intermediate geranylgeranyl pyrophosphate, which was produced by 3-hydroxy-3-methylglutaryl-CoA reductase, significantly restored the attenuated mTOR activity, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A expression and β-cell function after atorvastatin, lovastatin, rosuvastatin and fluvastatin treatment. [Diabetes] Abstract

Preparation of a New Type 2 Diabetic Miniature Pig Model via the CRISPR/Cas9 System

The authors obtained islet amyloid polypeptide gene-humanized miniature pigs via the CRISPR/Cas9 system and somatic cell nuclear transfer technology. The mature human islet amyloid polypeptide protein pigs could be used to further study the pathogenesis and related complications of type 2 diabetes mellitus and to lay a solid foundation for the prevention and treatment of type 2 diabetes mellitus. [Cell Death Dis] Full Article

GPR40 Activation Initiates Store-Operated Ca²⁺ Entry and Potentiates Insulin Secretion via the IP3R1/STIM1/Orai1 Pathway in Pancreatic β-Cells

Scientists showed that GPR40-mediated potentiation of glucose-induced insulin secretion was abolished by knockdown of IP3 receptor 1 (IP3R1), STIM1 or Ca²⁺-channel Orai1 in insulin-secreting MIN6 cells. STIM1 and Orai1 knockdown significantly impaired store-operated Ca²⁺ entry and the increase of intracellular Ca²⁺ by the GPR40 agonist, fasiglifam. [Sci Rep] Full Article

Pancreatic β-Cell-Specific Deletion of Insulin-Degrading Enzyme Leads to Dysregulated Insulin Secretion and β-Cell Functional Immaturity

Glucose-stimulated insulin secretion was quantified in isolated pancreatic islets and beta-cell differentiation markers and insulin secretion machinery were characterized by RT-PCR. Additionally, insulin-degrading enzyme was genetically and pharmacologically inhibited in INS-1E cells and rodent and human islets, and insulin secretion was assessed. [Am J Physiol Endocrinol Metab] Abstract

Inhibitory Effect of Oat Bran Ethanol Extract on Survival and Gemcitabine Resistance of Pancreatic Cancer Cells

The effects of oat bran ethanol extract on pancreatic cancer cells and gemcitabine-resistant pancreatic cancer cells were investigated in vitro. Oat bran ethanol extract decreased cell survival and colony forming ability of pancreatic cancer cells, without any cytotoxicity on the normal pancreatic cells. [Molecules] Full Article

PANCREATIC CANCER

Silencing of Neuropilins and GIPC1 in Pancreatic Ductal Adenocarcinoma Exerts Multiple Cellular and Molecular Antitumor Effects

Investigators directly compared the various tumor-inhibitory effects of transient RNAi-mediated depletion of Neuropilins-1 (NRP1), NRP2 and GAIP interacting protein C-terminus 1 (GIPC1), alone or in combination, in a set of cell lines with different expression levels. [Sci Rep] Full Article

Doxorubicin and Varlitinib Delivery by Functionalized Gold Nanoparticles against Human Pancreatic Adenocarcinoma

The cytotoxicity effect induced by the doxorubicin and varlitinib combination was investigated in pancreatic cancer cell lines. Doxorubicin and varlitinib conjugated with pegylated gold nanoparticles revealed a combined effect to decrease the cell survival of the cancer line S2-013s, while reducing the drugs’ toxicity for the healthy pancreatic cells hTERT-HPNE. [Pharmaceutics] Full Article

Coix Seed Extract Enhances the Anti-Pancreatic Cancer Efficacy of Gemcitabine through Regulating ABCB1- and ABCG2-Mediated Drug Efflux: A Bioluminescent Pharmacokinetic and Pharmacodynamic Study

The authors utilized bioluminescence imaging to monitor the ATP-binding cassette transporter mediated intracellular drug efflux function. They also investigated the potential association between the intracellular bioluminescent pharmacokinetic profiles and the anti-tumor efficacy of the coix seed extract and gemcitabine against pancreatic cancer cells in vitro and in vivo. [Int J Mol Sci] Full Article

Pharmacokinetic/Pharmacodynamic Modeling of the Anti-Cancer Effect of Dexamethasone in Pancreatic Cancer Xenografts and Anticipation of Human Efficacious Doses

Data of tumor growth profiles were collected from a patient-derived xenograft model in NOD/SCID mice and two cell line-derived xenograft models in BALB/c nude mice. Empirical pharmacokinetic/pharmacodynamic models were developed to establish mathematical relationships between plasma concentration of dexamethasone and tumor growth dynamics after integrating pharmacokinetic parameters extracted from literature. [J Pharm Sci] Abstract

Inhibition of TUG1/miRNA-299-3p Axis Represses Pancreatic Cancer Malignant Progression via Suppression of the Notch1 Pathway

Taurine-upregulated gene 1 (TUG1) and miR-299-3p expression profiles were measured by qRT-PCR. The direct interaction between TUG1 and miR-299-3p was explored by luciferase reporter assay. MTT assay, flow cytometry analysis, caspase-3 activity assay, Transwell invasion assay and wound healing assay were performed to evaluate cell proliferative ability, apoptosis, caspase-3 activity, invasion and migration, respectively. [Dig Dis Sci] Abstract

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Nutrient Metabolism, Subcellular Redox State and Oxidative Stress in Pancreatic Islets and β-Cells

Scientists present what is currently known about the compartmentation of redox homeostatic systems and tools to investigate it. They then review data about the effects of nutrients on β-cell subcellular redox state under normal conditions and in the context of type II diabetes, and discuss challenges and opportunities in the field. [J Mol Biol] Abstract

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

PharmaCyte Biotech to Change Future of Treating Diseases with Validation of Encapsulation Technology in Pancreatic Cancer Trial

PharmaCyte Biotech is closer than ever to its upcoming Phase IIb clinical trial in locally advanced, inoperable pancreatic cancer that could give patients a new lease on life by shrinking their tumors enough so that the tumors can be removed surgically. [PharmaCyte Biotech (GlobeNewswire, Inc.)] Press Release

Biomedical Professor Awarded $1.2 Million in Grants toward Diabetes Cure

Biomedical engineering professor Sha Jin at Binghamton University is trying to find a cure for diabetes from several different angles, and three federal grants received in August and September totaling nearly $1.2 million will aid her and her research team in that quest. [Binghamton University] Press Release

Academics in Ukraine Fighting Against Rampant Misconduct

Plagiarism, pseudoscience, bribes, and cheating. The threats to academia in Ukraine are many, according to false-science, a group of around 10 Ukrainian scientists dedicated to battling cheaters. [The Scientist] Editorial

White House to Host Closed-Door Summit on US Research Enterprise

The White House Office of Science and Technology Policy will host a one-day meeting in Washington, DC, to discuss a host of hot-button issues affecting the US research community. [ScienceInsider] Editorial

Beware the UK Government’s Brexit Promises

There’s a research group in Britain that has become a staple of the country’s news shows, and it’s called The UK in a Changing Europe. On most nights, the team of political scientists, economists and lawyers dispassionately responds to broadcasters’ questions on the impact — economic, political and societal — of the United Kingdom’s departure from the European Union. [Nature News] Editorial

NEW Gene Regulation: From Mechanisms to Disease
January 26-30, 2020
Keystone, United States

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

NEW Postdoctoral Researcher – Islet biology, Stem Cells and Regenerative Medicine (The Cell Isolation and Transplantation Center)

NEW Postdoctoral Fellow – Type I Diabetes Research (German Research Center for Environmental Health)

Studentship – Hormone Secretion in Islet Cells (Uppsala University)

Research Associate – Human Organogenesis (The University of Manchester)

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

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

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

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

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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