Pancreatic Cell News 8.20 May 23, 2017 | |
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TOP STORYStructure of the Full-Length Glucagon Class B G-Protein-Coupled Receptor The authors report the 3.0 Å crystal structure of full-length GCGR containing both the extracellular domain and transmembrane domain in an inactive conformation. The two domains are connected by a 12-residue segment termed the stalk, which adopts a β-strand conformation, instead of forming an α-helix as observed in the previously solved structure of the GCGR transmembrane domain. [Nature] Abstract | Press Release | |
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PUBLICATIONS(Ranked by impact factor of the journal)DIABETES & PANCREATITISHuman GLP-1 Receptor Transmembrane Domain Structure in Complex with Allosteric Modulators Scientists report crystal structures of the human glucagon-like peptide-1 receptor (GLP-1R) transmembrane domain in complex with two different negative allosteric modulators, PF-06372222 and NNC0640, at 2.7 and 3.0 Å resolution, respectively. The structures reveal a common binding pocket for negative allosteric modulators, present in both GLP-1R and glucagon receptor 3 and located outside helices V–VII near the intracellular half of the receptor. [Nature] Abstract | Press Release Radiomanganese PET Detects Changes in Functional β-Cell Mass in Mouse Models of Diabetes The authors investigated the whole-body distribution of 52Mn2+ in healthy adult mice by dynamic and static PET imaging. Pancreatic voltage-dependent Ca2+ channel uptake of 52Mn2+ was successfully manipulated pharmacologically in vitro and in vivo using glucose, nifedipine, the sulfonylureas tolbutamide and glibenclamide, and diazoxide. [Diabetes] Abstract Researchers investigated potential interactions between insulin and glucagon-like peptide (GLP)-1 signaling pathways in the regulation of beta cell-cycle dynamics in vivo, in the context of the therapeutic potential of GLP-1 to modulate impaired beta cell function. [Diabetologia] Abstract Scientists presented a comprehensive proteome profiling of isolated brain MAM from long-term type 2 diabetic mice vs. non-diabetic controls. The MAM protein was extracted efficiently by a surfactant-aided precipitation/on-pellet digestion method, and the MAM proteome was quantified by an ion-current-based MS1 method combined with nanoLC-MS/MS. [Sci Rep] Full Article PANCREATIC CANCERSuccession of Transiently Active Tumor-Initiating Cell Clones in Human Pancreatic Cancer Xenografts The authors showed that long‐term progression of pancreatic adenocarcinoma in serial xenotransplantation is driven by a succession of transiently active tumor‐initiating cells (TICs) producing tumor cells in temporally restricted bursts. Clonal tracking of individual, genetically marked TICs revealed that individual tumors are generated by distinct sets of TICs with very little overlap between subsequent xenograft generations. [EMBO Mol Med] Full Article Prolonged Exposure to Extracellular Lumican Restrains Pancreatic Adenocarcinoma Growth Investigators observed that extracellular lumican decreases pancreatic ductal adenocarcinoma (PDAC) tumor cell growth in xenograft and syngeneic orthotopic animal models, and induces growth inhibition of low-passage human PDAC cells in a species-specific manner. PDAC cells grown in variant culture conditions and exposed to extracellular lumican display typical characterizations of cancer cell in a quiescent state, such as growth inhibition, apoptosis, G0/G1 arrest and chemoresistance. [Oncogene] Abstract Stroma-Regulated HMGA2 Is an Independent Prognostic Marker in PDAC and AAC Researchers analyzed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adenocarcinoma (AAC) for HMGA2 expression by IHC. The data were correlated with stroma abundance and supplemented by experimental studies. [Br J Cancer] Abstract Scientists report that acid-sensing ion channel (ASIC) 1 and ASIC3 are mainly expressed on membrane of pancreatic cancer cells and upregulated in pancreatic cancer tissues. ASIC1 and ASIC3 are responsible for an acidity-induced inward current, which is required for elevation of intracellular Ca2+ concentration. [Cell Death Dis] Full Article Researchers developed novel peptide-based nanocomplexes for delivery of anti-miRNA oligonucleotides to human-derived pancreatic stellate cells, precursors of cancer-associated fibroblasts. [Nanomedicine (Lond)] Abstract | Graphical Abstract | |
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REVIEWSEndocrine-Disrupting Chemicals and the Regulation of Energy Balance The authors review the main mechanisms used by metabolism-disrupting chemicals (MDCs) to alter energy balance. This work should help to identify new MDCs, as well as novel targets of their action. [Nat Rev Endocrinol] Abstract The Role of PYY in Pancreatic Islet Physiology and Surgical Control of Diabetes Scientists discuss recent findings on peptide tyrosine tyrosine (PYY)-mediated control of glucose homeostasis and its role in diabetes, in the context of what is known for GLP-1. Identification of factors that increase the expression of PYY following bariatric surgery and elucidation of its role in diabetes reversal may have clinical relevance as a nonsurgical therapy for type 2 diabetes. [Trends Endocrinol Metab] Abstract Visit our reviews page to see a complete list of reviews in the pancreatic cell research field. | |
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INDUSTRY NEWSViaCyte, Inc. and JDRF jointly announced JDRF grant funding to support the development of the PEC-Direct™ islet cell replacement therapy being developed for type 1 diabetes patients with severe life-threatening hypoglycemia unawareness and related risks. [ViaCyte, Inc.] Press Release Fractyl Laboratories Inc. announced that the first patient in Europe has been treated as part of a clinical trial called Revita-2. The trial is designed to evaluate the safety and efficacy of the Revita™ DMR System in orally-treated type 2 diabetes patients with poorly controlled disease. [Fractyl Laboratories Inc.] Press Release ViaCyte, Inc. announced that the U.S. Food and Drug Administration (FDA) has allowed the company’s Investigational New Drug Application (IND) for the PEC-Direct™ product candidate, a novel islet cell replacement therapy in development as a potential cure for patients with type 1 diabetes who are at high risk for acute life-threatening complications. ViaCyte has also received a No Objection Letter from Health Canada, providing clearance to proceed with the clinical trial of the PEC-Direct product candidate in Canada as well. [ViaCyte, Inc.] Press Release EnteroMedics Inc. announced that the McGuire Veterans Affairs Medical Center in Richmond, VA successfully completed its first implant of the company’s vBloc® Neurometabolic Therapy. The surgery was performed earlier this week by James Maher, MD. [EnteroMedics Inc.] Press Release | |
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POLICY NEWSWhat’s in Trump’s 2018 Budget Request for Science? President Donald Trump unveiled his full 2018 budget request to Congress. The spending plan, for the fiscal year that begins 1 October, fleshes out the so-called skinny budget that the White House released this past March. That plan called for deep cuts to numerous research agencies. [ScienceInsider] Editorial UK Political Parties Promise Science Funding Boost UK scientists worried about how Brexit will affect their funding received a boost when the country’s three main national parties pledged long-term targets to raise research spending. [Nature News] Editorial Journal that Holds Record for Retracted Papers Also Has a Problem with Editorial Board Members Last month, Springer, announced that the journal Tumor Biology was retracting 107 papers after finding that the peer-review process had been compromised. It was the third mass retraction at Tumor Biology. But that’s not Tumor Biology’s only problem. ScienceInsider has discovered that the journal’s editorial board, as published online, contains the names of several scientists who say they have no relationship whatsoever with the journal—including German Nobel laureate Harald zur Hausen. [ScienceInsider] Editorial
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EVENTSNEW Growth Hormone/Prolactin Family in Biology and Disease Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESPostdoctoral Fellowship – Diabetes UK (Diabetes UK) PhD Studentship – Diabetes UK (Diabetes UK) Bioinformatician – Genomic Programming of Beta Cells (Imperial College London) Research Leaders – Career Development Award or Tenure Track (Medical Research Council) Postdoctoral Fellow – Diabetes (University of Toronto) Postdoctoral Associate – Pancreatic Beta Cells (Johns Hopkins School of Medicine) Faculty Member – Endocrinology, Diabetes and Metabolism (Johns Hopkins University) Postdoctoral Fellow – Diabetes Research (Child Health Institute of New Jersey) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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Home Pancreatic Cell News Volume 8.20 | May 23 2017