Pancreatic Cell News Volume 9.40 | Oct 9 2018

TOP STORY

Levels of the Autophagy Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice

Cultured heterozygous disruption of autophagy related 5 primary tumor cells were resistant to induction and inhibition of autophagy, had altered mitochondrial morphology, compromised mitochondrial function, changes in intracellular Ca²⁺ oscillations, and increased activity of extracellular cathepsin L and D. [Gastroenterology] Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Preserving Insulin Secretion in Diabetes by Inhibiting VDAC1 Overexpression and Surface Translocation in β Cells

Voltage-dependent anion channel-1 (VDAC1) overexpression caused its mistargeting to the plasma membrane of insulin-secreting β cells with loss of the crucial metabolic coupling factor ATP. Through direct inhibition of VDAC1 conductance, metformin, like specific VDAC1 inhibitors and antibodies, restored the impaired generation of ATP and glucose-stimulated insulin secretion in type 2 diabetes islets. [Cell Metab] Abstract | Press Release | Graphical Abstract

Complement Component C3 Is Highly Expressed in Human Pancreatic Islets and Prevents β Cell Death via ATG16L1 Interaction and Autophagy Regulation

Researchers showed that human pancreatic islets highly expressed C3, which is both secreted and present in the cytosol. C3 interacted with ATG16L1, which is essential for autophagy. C3 knockout in clonal β cells impaired autophagy and led to increased apoptosis after exposure of cells to palmitic acid and IAPP. In the absence of C3, autophagosomes did not undergo fusion with lysosomes. [Cell Metab] Abstract | Press Release | Graphical Abstract

RNA-Binding Protein DDX1 Is Responsible for Fatty Acid-Mediated Repression of Insulin Translation

Investigators showed that palmitate treatment caused DDX1 phosphorylation at S295 and dissociated DDX1 from insulin mRNA, thereby leading to the suppression of insulin translation. [Nucleic Acids Res] Full Article

Genome-Wide Profiling of Histone H3K27 Acetylation Featured Fatty Acid Signaling in Pancreatic Beta Cells in Diet-Induced Obesity in Mice

Scientists found that INS-1 cells exhibited downregulation of fatty acid β-oxidation genes in parallel with decrease in the associated histone H3 lysine 27 acetylation (H3K27ac). Palmitate treatment caused increase in H3K27ac and induction of β-oxidation genes; these responses were blunted when nuclear respiratory factor 1, GA repeat binding protein α or myocyte enhancer factor 2A were suppressed. [Diabetologia] Abstract

C-Terminal Degradation of PYY Peptides in Plasma Abolishes Effects on Satiety and Beta-Cell Function

Peptide YY (PYY)(1-36) and PYY(3-36) inhibited glucose- and alanine-stimulated insulin secretion from BRIN-BD11 beta-cells. Both PYY(1-36) and PYY(3-36), but not related PYY metabolites, significantly enhanced proliferation of BRIN BD11 and 1.1B4 beta-cell lines, and protected these cell lines against cytokine-induced apoptosis. [Biochem Pharmacol] Abstract | Graphical Abstract

PDL1 Is Expressed in the Islets of People with Type 1 Diabetes and Is Up-Regulated by Interferons-α and-γ via IRF1 Induction

Interferons-α and -γ, but not interleukin-1β, induced PDL1 expression in vitro in human islet cells and EndoC-βH1 cells. Silencing of STAT1 or STAT2 individually did not prevent interferon-α-induced PDL1, while blocking of JAKs – a proposed therapeutic strategy for type 1 diabetes – or IRF1 prevented PDL1 induction. [EBioMedicine] Full Article

PANCREATIC CANCER

Hypoxia-Induced Autophagy of Stellate Cells Inhibits Expression and Secretion of Lumican into Microenvironment of Pancreatic Ductal Adenocarcinoma

Investigators observed that hypoxia significantly reduced lumican expression and secretion from pancreatic stellate cells, but not cancer cells. Although hypoxia enhanced lactate dehydrogenase A expression and lactate secretion from all cells, neither hypoxia-induced nor exogenous lactate influenced lumican expression. [Cell Death Differ] Abstract

Mutant p53 Prevents GAPDH Nuclear Translocation in Pancreatic Cancer Cells Favoring Glycolysis and 2-Deoxyglucose Sensitivity

Researchers demonstrated that mutant p53 prevented the nuclear translocation of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) stabilizing its cytoplasmic localization, thus supporting glycolysis of cancer cells and inhibiting cell death mechanisms mediated by nuclear GAPDH. [BBA-Mol Cell Res] Full Article

An ABCG2 Non-Substrate Anticancer Agent FL118 Targets Drug-Resistant Cancer Stem-Like Cells and Overcomes Treatment Resistance of Human Pancreatic Cancer

Scientists found that FL118 alone preferentially killed cisplatin-resistant cancer cells, while a combination of FL118 with cisplatin synergistically killed resistant pancreatic cancer cells and reduced spheroid formation of treatment-resistant pancreatic cancer stem-like cells. [J Exp Clin Cancer Res] Full Article

Subscribe to one of our other 19 science newsletters such as Hepatic Cell News & Intestinal Cell News.

Glucose Homeostasis Dependency on Acini-Islet-Acinar (AIA) Axis Communication: A New Possible Pathophysiological Hypothesis regarding Diabetes Mellitus

The authors introduce the concept of AIA axis communication, which could play an important role in the development of obesity and diabetes type 2. The AIA feedback links the endocrine and exocrine parts of the pancreas and emphasizes the essential role that the pancreas plays, as a single organ, in the regulation of glucose homeostasis by amylase most probably in gut epithelium and by insulin and glucagon in peripheral blood. [Nutr Diabetes] Full Article

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

NOXXON Presents Top-Line Data From NOX-A12 Monotherapy Part of Ongoing Metastatic Colorectal and Pancreatic Cancer Trial

NOXXON Pharma N.V. announced that it presented top-line data of the ongoing clinical trial testing NOX-A12 alone and available safety data from the combination of NOX-A12 with Merck & Co./MSD’s Keytruda^® in patients with metastatic, microsatellite-stable pancreatic and colorectal cancer. [Press release from NOXXON Pharma discussing research presented at the 4^th CRI-CIMT-EATI-AACR International Cancer lmmunotherapy Conference, New York] Press Release

Boehringer Ingelheim and Lilly Present Full Results from EASE Phase III Program for Empagliflozin as Adjunct to Insulin in Type 1 Diabetes

Boehringer Ingelheim and Eli Lilly and Company announced that empagliflozin met the primary efficacy endpoint, defined as a change from baseline in A1C versus placebo after 26 weeks of treatment, for all doses investigated in the Empagliflozin as Adjunctive to inSulin thErapy (EASE) Phase III program in adults with type 1 diabetes. [Press release from Eli Lilly discussing research presented at the 54^th EASD Annual Congress, Berlin] Press Release

New Data on Effect of Anti-Obesity Agent Belviq^® on Prevention and Remission of Type 2 Diabetes Presented

Eisai Co., Ltd. announced that new data on prevention and remission of type 2 diabetes mellitus from the long-term Cardiovascular Outcomes Trial in patients treated with lorcaserin hydrochloride were presented. [Press release from Eisai Co., Ltd discussing research presented at the 54^th EASD Annual Congress, Berlin] Press Release

MannKind Presents Positive Afrezza^® STAT Study Clinical Data

MannKind Corporation presented data from the STAT study (STudy comparing prandial insulin Aspart vs. Technosphere insulin in patients with type 1 diabetes on multiple daily injections). [Press release from MannKind Corporation discussing research presented at the 54^th EASD Annual Congress, Berlin] Press Release

Poxel Announces Completion of Patient Enrollment for TIMES 2 Trial in Phase III Registration Program for Imeglimin, an Investigational Therapeutic Agent for Type 2 Diabetes, in Japan

POXEL SA announced that patient enrollment has been completed in the TIMES 2 trial of the Phase III registration program for Imeglimin, an investigational therapeutic agent for type 2 diabetes, in Japan. [POXEL SA] Press Release

International Diabetes Study Receives SEK 40 Million to Continue

The TEDDY Study has increased our knowledge about what happens prior to the onset of autoimmune diabetes and has shown that a stomach infection can trigger celiac disease. Lund University in Sweden has now received just over SEK 40 million from the American National Institutes of Health to continue the TEDDY Study for another five years. [Lund University] Press Release

Beta Bionics Awarded Up to $2 Million NIH Small Business Innovation Research (SBIR) Grant

Beta Bionics, Inc. announced that it has been awarded up to $2 million in the form of an SBIR grant by the NIDDK, which is part of the U.S. National Institutes of Health. [Beta Bionics (GlobeNewswire, Inc.)] Press Release

Was Cancer Scientist Fired for Challenging Lab Chief over Authorship?

Rutgers University terminated a veteran cancer scientist in retaliation, the researcher says, for challenging a powerful principal investigator on the authorship of a paper apparently accepted for publication in Nature. The researcher is now deciding whether to appeal her dismissal in arbitration through her union or to sue Rutgers. [ScienceInsider] Editorial

Industry Partners Extensively Involved in Trials They Fund

Industry funders are usually involved in every stage of the clinical trials they support, and may try to downplay their involvement when trial results are reported, according to a study led by researchers in Denmark published in BMJ. The findings suggest that industry funders may be wielding greater influence over how trials are conducted and how results are published than currently realized. [The Scientist] Editorial

Questions about Funding and Purpose Loom over a Foundation Congress Created to Help the FDA

The Reagan-Udall Foundation for the FDA is supposed to act as a liaison between the FDA itself and drug companies, researchers, nonprofits, or other businesses with regulated products who might want to support a project to make the agency’s job easier. It has raised just under $15 million during its first decade, according to the foundation. [STAT News] Editorial

NEW AACR: The Hippo Pathway: Signaling, Cancer, and Beyond
May 8-11, 2019
San Diego, California, United States

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

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

Research Technologist – Pancreatic (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Islet Biology (University of Alberta)

Postdoctoral Researcher – Identifying Cell Surface Receptor (Ionis Pharmaceuticals, Inc.)

Postdoctoral Position – Metabolic Inflammation in Diabetes (Inserm)

Assistant Professor – Biomedical Sciences (New York Institute of Technology)

Scientists – Diabetes Research (Qatar Biomedical Research Institute)

Postdoctoral Position – Human Microphysiology Systems of Pancreatic Islets (University of Pittsburgh Drug Discovery Institute)

Caspar Wistar Fellows – Cancer Biology (The Wistar Institute)

Postdoctoral Researcher – Diabetes Research (UC San Diego School of Medicine)

Postdoctoral Positions – Immunology of Diabetes (Cochin Institute)

Postdoctoral Position – Inflammation and Metabolism (Sanford Burnham Prebys Medical Discovery Institute)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Pancreatic Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.