Pancreatic Cell News Volume 8.28 | Jul 18 2017

TOP STORY

Loss of mTORC1 Signaling Impairs β-Cell Homeostasis and Insulin Processing

The authors showed that β-cell-specific loss of mTOR complex 1 (mTORC1) causes diabetes and β-cell failure due to defects in proliferation, autophagy, apoptosis and insulin secretion by using mice with conditional and inducible raptor deletion. Through genetic reconstitution of mTORC1 downstream targets, they identified the mTORC1/S6K pathway as the mechanism by which mTORC1 regulates β-cell apoptosis, size and autophagy, whereas mTORC1/4E-BP2-eIF4E pathway regulates β-cell proliferation. [Nat Commun] Full Article

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DIABETES & PANCREATITIS

Defining a Novel Role for the PDX1 Transcription Factor in Islet β Cell Maturation and Proliferation during Weaning

Because of the presence in Area IV of binding sites for transcription factors associated with pancreas development and islet cell function, researchers analyzed how an endogenous deletion mutant affected Pdx1 expression embryonically and postnatally. The most striking result was observed in male Pdx1^ΔIV mutant mice after three weeks of birth, with only a small effect on pancreas organogenesis and no deficiencies in their female counterparts. [Diabetes] Abstract

Thyroid Hormone Coordinates Pancreatic Islet Maturation during the Zebrafish Larval to Juvenile Transition to Maintain Glucose Homeostasis

Scientists used the zebrafish as a model to test whether and how thyroid hormone (TH) signaling affects pancreatic islet maturation, and consequently glucose homeostasis, during the larval to juvenile transition. They found that exogenous TH precociously activates the β cell differentiation genes pax6b and mnx1, while downregulating arxa, a master regulator of α cell development and function. [Diabetes] Abstract

PIWI-Interacting RNAs as Novel Regulators of Pancreatic Beta Cell Function

Investigators identified the P-element induced Wimpy testis (PIWI)-interacting RNAs (piRNAs) expressed in pancreatic islets and determined whether they are involved in the control of beta cell activities. They identified changes in the level of several piRNAs in the islets of Goto–Kakizaki rats, a well-established animal model of type 2 diabetes. [Diabetologia] Abstract

RIP3 Attenuates the Pancreatic Damage Induced by Deletion of ATG7

Researchers investigated whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Mice deficient for pancreatic Atg7 developed acute pancreatitis, which progressed to chronic pancreatitis. [Cell Death Dis] Full Article

Platelet-Derived Mitochondria Display Embryonic Stem Cell Markers and Improve Pancreatic Islet β-Cell Function in Humans

Four-year follow-up studies demonstrated the long-term safety and clinical efficacy of Stem Cell Educator therapy for the treatment of type 1 diabetes and type 2 diabetes. Using freshly-isolated human pancreatic islets, ex vivo studies established that platelet-releasing mitochondria can migrate to pancreatic islets and be taken up by islet β cells, leading to the proliferation and enhancement of islet β-cell functions. [Stem Cells Transl Med] Full Article

PANCREATIC CANCER

Hypoxia-Inducible Factor-2α Promotes Tumor Progression and Has Crosstalk with Wnt/β-Catenin Signaling in Pancreatic Cancer

The authors used a mutated hypoxia-inducible factor (hif)-2α to figure out the problem that wild-type hif-2α is quickly degraded, which limits the study of its function. Using several cell lines, mouse models, and human tissues, they obtained a general picture of hif-2α in pancreatic cancer progression. [Mol Cancer] Full Article

HMGA1 Expression Levels Are Elevated in Pancreatic Intraepithelial Neoplasia Cells in the Ptf1a-Cre; LSL-KrasG12D Transgenic Mouse Model of Pancreatic Cancer

High-mobility group A1 protein (HMGA1) is an oncogenic transcription factor, localized and active in cell nuclei, that is linked to tumor progression in many human cancers, including pancreatic cancer. Overexpression of HMGA1 renders cancer cells resistant to chemotherapy. Quantitative immunohistochemical analysis was used to determine nuclear HMGA1 levels in pancreatic tissue sections from Ptf1a-Cre; LSL-KrasG12D mice. [Br J Cancer] Abstract

Linc-DYNC2H1-4 Promotes EMT and CSC Phenotypes by Acting as a Sponge of miR-145 in Pancreatic Cancer Cells

Investigators identified which factor could promote epithelial-mesenchymal transition (EMT) and cancer stem-like cell (CSC) formation and uncover the mechanistic role of such factor is important for novel and targeted therapies. They found that the long intergenic non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC-3-Gem with acquired gemcitabine resistance. [Cell Death Dis] Full Article

Exosomes Derived from Pancreatic Cancer Cells Induce Insulin Resistance in C2C12 Myotube Cells through the PI3K/Akt/FoxO1 Pathway

Scientists explored the effects of two types of exosomes released by murine pancreatic cancer and ductal epithelial cells on murine skeletal muscle cells. The results showed that pancreatic cancer-derived exosomes can readily enter C2C12 myotubes, triggering lipidosis and glucose intake inhibition. [Sci Rep] Full Article

The lncRNA MALAT1 Acts as a Competing Endogenous RNA to Regulate KRAS Expression by Sponging miR-217 in Pancreatic Ductal Adenocarcinoma

Researchers investigated the role of metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) in pancreatic ductal adenocarcinoma (PDAC). MALAT1 was expressed at higher levels in PDAC tissues than in nontumor tissues and in metastatic PDAC than in localized tumors. [Sci Rep] Full Article

Animal Models of Human Type 1 Diabetes for Evaluating Combination Therapies and Successful Translation to the Patient with Type 1 Diabetes

The advantages and disadvantages of the three spontaneous rat models and the NOD mouse, compared to the characteristics of human type 1 diabetes, are considered. [Diabetes Metab Res Rev] Abstract

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Abbott and Bigfoot Biomedical Announce Collaboration to Develop Breakthrough Diabetes Technologies

Abbott and Bigfoot Biomedical announced that the companies have entered into an agreement to develop and commercialize diabetes management systems, integrating Abbott’s FreeStyle^® Libre glucose sensing technology with Bigfoot’s insulin delivery solutions in the United States. [Abbott] Press Release

Lustgarten Foundation to Commit $40 Million to Pancreatic Cancer Research in 2017-18

The Lustgarten Foundation announced that it will commit an unprecedented $40 million in 2017-18 through its new Translational Clinical Program, expanded Research Investigator Award Program and other partnerships. This is the first time any pancreatic cancer organization will commit that level of funding in a condensed period of time. [The Lustgarten Foundation] Press Release

Provention Bio, Inc. Announces Clinical Program Focused on Intercepting and Preventing the Onset of Type 1 Diabetes

Provention Bio, Inc. announced the in-licensing of an enterovirus vaccine platform, which the company is initially developing to reduce the onset of type 1 diabetes by vaccinating at-risk populations against coxsackievirus B infection. [Provention Bio, Inc.] Press Release

NYU Langone Launches Major Interdisciplinary Program Targeting Pancreatic Cancer

Perlmutter Cancer Center at NYU Langone has announced the creation of a multidisciplinary center of excellence to develop innovative approaches to diagnose, treat, and prevent pancreatic cancer. [NYU Langone Medical Center] Press Release

Relatively Few NIH Grantees Get Lion’s Share of Agency’s Funding

The rich have been getting richer in the biomedical research enterprise, and the system favors those who are already doing pretty well, according to a new analysis of National Institutes of Health (NIH) grant recipients. [ScienceInsider] Editorial

Two Female Scientists Sue Salk Institute, Alleging Discrimination at ‘Old Boys Club’

Two senior female scientists are suing their employer, the prestigious Salk Institute for Biological Studies, alleging pervasive, long-standing gender discrimination. In the pair of lawsuits, filed in California Superior Court in San Diego, plaintiffs Vicki Lundblad and Katherine Jones seek unspecified compensation for an array of harms. [ScienceInsider] Editorial

To Woo Public, Europe Opens Up on Animal Experiments, but U.S. Less Transparent

A London-based group that supports the use of animals in biomedical science began inviting the public to take an unusual digital tour of laboratories at four U.K. research institutions. At LabAnimalTour.org, users can watch a monkey with a bolt in its skull forage in its cage at a University of Oxford neuroscience lab and a technician check on some of the 8000 mice housed in one room at the Medical Research Council’s Harwell Institute. [ScienceInsider] Editorial

Why a Flat 2018 Budget Could Tie NSF’s Hands

What would a flat budget mean for the National Science Foundation (NSF)? For many agencies, it means maintaining the status quo. And NSF may have trouble doing anything other than that thanks to some pointed instructions from a key legislator. [ScienceInsider] Editorial

NEW Tumor Immunology and Immunotherapy
October 1-4, 2017
Boston, Massachusetts, United States

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NEW Postdoctoral Researcher – Obesity and Diabetes (University of Iowa)

NEW Assistant Professor – Metabolic Disorders (Umeå University)

PhD Position – Proteomics, 3D Cell Culture and Pancreatic Beta Cells Plasticity (University of Southern Denmark)

Senior Scientific Officer – Pancreatic Cancer (Cancer Research UK Beatson Institute)

Senior/Principal Scientist – Stem Cell Research (Plasticell Ltd)

Postdoctoral Fellow – Integrative Computational Biology (Wellcome Trust Sanger Institute)

Group Leader – Cancer Research (University of Lille)

Postdoctoral Research Fellow – Pancreatic Cancer (Fred Hutchinson Cancer Research Center)

PhD Position – Insulin Storage (Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences)

PhD Position – Health/Biomedical Sciences (University of Auckland)

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