Pancreatic Cell News Volume 10.22 | Jun 11 2019

TOP STORY

Cells Deploy a Two-Pronged Strategy to Rectify Misfolded Proinsulin Aggregates

Researchers report that Akita mutant proinsulin formed detergent-insoluble aggregates that entrapped wild-type proinsulin in the endoplasmic reticulum, thereby blocking insulin production. [Mol Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Diabetes Causes Marked Inhibition of Mitochondrial Metabolism in Pancreatic β-Cells

INS-1 β-cells cultured chronically at high glucose showed changes in protein expression and reduced glucose-stimulated oxygen consumption; targeted metabolomics revealed impaired metabolism. [Nat Commun] Full Article

Differential Effect of Glucose on ER-Mitochondria Ca²⁺ Exchange Participates to Insulin Secretion and to Glucotoxicity-Mediated Dysfunction of β Cells

Researchers report that acute glucose stimulation stimulated endoplasmic reticulum (ER)-mitochondria interactions and calcium (Ca²⁺) exchange in INS-1E cells, whereas disruption of mitochondria-associated membranes altered glucose-stimulated insulin secretion. [Diabetes] Abstract

Pancreatic Beta Cells Persistently Infected with Coxsackievirus B₄ Are Targets of NK Cell-Mediated Cytolytic Activity

A persistent coxsackieviruses-B infection was established in 1.1B₄ pancreatic beta cells. The proportion of cells containing viral protein VP1 was low, although a large proportion of cells harbored viral RNA, whilst cell viability was preserved. [Cell Mol Life Sci] Abstract

Sonodynamic Therapy Inhibits Palmitate-Induced Beta Cell Dysfunction via PINK1/Parkin-Dependent Mitophagy

A beta cell injury model was established with palmitic acid to simulate the lipotoxicity found in type 2 diabetes mellitus. Sonodynamic therapy, a novel physicochemical treatment, was applied to treat injured beta cells. [Cell Death Dis] Full Article

Targeting CLDN18.2 by CD3 Bispecific and ADC Modalities for the Treatments of Gastric and Pancreatic Cancer

Anti-human (h) CLDN18.2 ADC, CD3-bispecific and diabody, targeting a protein sequence conserved in rat, mouse and monkey, exhibited in vitro cytotoxicity in BxPC3/hCLDN18.2 and KATO-III/hCLDN18.2 respectively and inhibited tumor growth of pancreatic and gastric patient-derived xenograft tumors. [Sci Rep] Full Article

PANCREATIC CANCER

A Novel Oxoglutarate Dehydrogenase-Like Mediated miR-214/TWIST1 Negative Feedback Loop Inhibits Pancreatic Cancer Growth and Metastasis

Oxoglutarate dehydrogenase like (OGDHL) was downregulated in human pancreatic cancer and predicted poor prognosis. OGDHL overexpression inhibited migration and invasion of pancreatic cancer cells and suppressed pancreatic cancer tumor growth. [Clin Cancer Res] Abstract | Full Article

TMEM16A Controls EGF-Induced Calcium Signaling Implicated in Pancreatic Cancer Prognosis

In vitro, TMEM16A was required for EGF-induced store-operated calcium entry essential for pancreatic cancer cell migration. TMEM16A also had a profound impact on phosphoproteome remodeling upon EGF stimulation. [Proc Natl Acad Sci USA] Abstract

Genetic Ablation of the Cystine Transporter xCT in PDAC Cells Inhibits mTORC1, Growth, Survival and Tumor Formation via Nutrient and Oxidative Stresses

The authors explored the potential of targeting cystine/glutamate exchanger (SLC7A11/xCT), which contributed to the maintenance of intracellular glutathione. Genomic disruption of xCT via CRISPR-Cas9 was achieved in two pancreatic ductal adenocarcinoma (PDAC) cell lines and xCT-KO clones were cultivated in the presence of N-acetylcysteine. [Cancer Res] Abstract | Full Article

Aberrant NFATc1 Signaling Counteracts TGFβ-Mediated Growth Arrest and Apoptosis Induction in Pancreatic Cancer Progression

In contrast to previous reports and consistent with a concept of retained tumor suppressive transforming growth factor β (TGFβ) activity, even in established pancreatic ductal adenocarcinoma (PDAC), TGFβ treatment reduced PDAC cell proliferation and promoted apoptosis even in the presence of oncogenic nuclear factor of activated T cells (NFATc1). [Cell Death Dis] Full Article

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Tools for Bioimaging Pancreatic β Cells in Diabetes

The authors explore the need to bioimage human β cells noninvasively in various types of diabetes, and they discuss current and emerging tools for bioimaging β cells. [Trends Mol Med] Abstract

Platelets as Potent Signaling Entities in Type 2 Diabetes Mellitus

Investigators highlight how circulating inflammatory molecules, acting as platelet receptor ligands, interact with platelets, causing platelets to be potent drivers of systemic inflammation. [Trends Endocrinol Metab] Abstract

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

Protokinetix Achieves Primary Objective Safety at Midpoint of Clinical Trial

ProtoKinetix, Incorporated announced reaching the midpoint of a Phase I first-in-human clinical trial of AAGP™ PKX-001 treated islet cells used in conjunction with the Edmonton Protocol for the treatment of Type-1 diabetes. [ProtoKinetix, Inc.] Press Release

Adocia Initiates a Three-Week Phase Ib Study of ADO09, a Co-Formulation of Pramlintide and Mealtime Insulin, in People with Type 1 Diabetes

Adocia announced the initiation of a Phase Ib study of ADO09, a ready-to-use, fixed ratio co-formulation of pramlintide, the only FDA-approved analog of amylin, and A21G human insulin analog, a rapid-acting insulin that is known to be the main circulating metabolite of insulin glargine. [Adocia] Press Release

Beta Bionics and Zealand Pharma Announce Superior Glycemic Control in Phase II Home-Use Clinical Trial Testing the iLet™ Bionic Pancreas Using Dasiglucagion

Beta Bionics, Inc. and Zealand Pharma A/S announced that a home-use study of dasiglucagon in the iLet™ Bionic Pancreas System has been successfully completed. [Beta Bionics, Inc. (GlobeNewswire, Inc.)] Press Release

Cotinga Pharmaceuticals Announces Initiation of Next Cohort of Phase Ib/IIa Combination Trial of COTI-2 in Solid Tumors

Cotinga Pharmaceuticals Inc. announced that it has initiated the third cohort of its ongoing Phase Ib/IIa clinical trial of COTI-2 plus cisplatin in solid tumors. [Cotinga Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release

Sudanese Academics Defiant as Revolution Turns Bloody

Sudan’s universities are shut, flights have been suspended and the Internet remains almost entirely blocked after a brutal crackdown in which paramilitaries are thought to have killed some 100 pro-democracy protestors. But none of this has dented the resolve of the protestors, whose ranks include several prominent academics and whose demands include freeing universities from government influence. [Nature News] Editorial

Wellcome Sanger Institute to Close Animal Facility

The Wellcome Sanger Institute announced that it would be closing its animal facility, which provides mice, zebrafish, rats, and frogs to geneticists at the institute and internationally, reports Nature. The institute states that the closure is related to the growing use of cell lines and organoids, instead of animals. [The Scientist] Editorial

NEW European Congress on Clinical and Translational Medicine (EUSTM)
October 18-20, 2019
Vienna, Austria

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

NEW PhD Student – Diabetes (University of Edinburgh)

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

Scientist – Genetic and Genomic Epidemiology (International Agency for Research on Cancer)

Postdoctoral Fellow – Preclinical Cancer Research (Karolinska Institutet)

Postdoctoral Research Scientist – Regeneration of Insulin-Producing β-Cells (MRC London Institute of Medical Sciences)

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

Professor – Diabetes Research (University of Tennessee Health Science Center)

Postdoctoral Fellowship – Pancreatic Cancer (Oregon Health and Science University)

Postdoctoral Fellowship – Regenerative Medicine (Cornell University)

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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