Pancreatic Cell News Volume 7.25 | Jun 28 2016

TOP STORY

Novel Gene-Hunting Method Implicates New Culprit in Pancreatic Cancer

Using an innovative approach to identify a cancer’s genetic vulnerabilities by more swiftly analyzing human tumors transplanted into mice, researchers have identified a new potential target for pancreatic cancer treatment. The team found the gene WDR5 protects pancreatic tumors from DNA damage, working with the previously known cancer-promoting gene called Myc to help tumors thrive. [Press release from the University of Texas MD Anderson Cancer Center discussing online prepublication in Cell Reports] Press Release | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

CART Is Overexpressed in Human Type 2 Diabetic Islets and Inhibits Glucagon Secretion and Increases Insulin Secretion

Researchers report an important role of cocaine-and amphetamine-regulated transcript (CART, encoded by Cartpt) in human islet function and glucose homeostasis in mice. CART was found to be expressed in human alpha and beta cells and in a subpopulation of mouse beta cells. Notably, CART expression was several fold higher in islets of type 2 diabetic humans and rodents. [Diabetologia] Abstract

RIG-I Inhibits Pancreatic β Cell Proliferation through Competitive Binding of Activated Src

Scientists showed that retinoic acid-inducible gene I (RIG-I) responds to nutrient signals and induces loss of β cell mass through G1 cell cycle arrest. Risk factors for type 2 diabetes (e.g., glucolipotoxicity, TNF-α and LPS) activate Src in pancreatic β cells. [Sci Rep] Full Article

STAT3 Modulates β-Cell Cycling in Injured Mouse Pancreas and Protects against DNA Damage

Duct ligation stimulates the expression of several cytokines that can act as ligands inducing STAT3 signaling and phosphorylation in β-cells. β-Cell cycling increased by conditional β-cell-specific Stat3 knockout and decreased by STAT3 activation through administration of interleukin-6. In addition, the level of DNA damage in β-cells of pancreatic duct ligation pancreas increased after deletion of Stat3. [Cell Death Dis] Full Article

Junctophilin 3 Expresses in Pancreatic Beta Cells and Is Required for Glucose-Stimulated Insulin Secretion

Researchers investigated whether junctophilins are involved in the proper communication between Ca²⁺ influx and subsequent Ca²⁺ amplification in pancreatic beta cells, thereby participating in regulating insulin secretion. [Cell Death Dis] Full Article

Oleate Protects Beta-Cells from the Toxic Effect of Palmitate by Activating Pro-Survival Pathways of the ER Stress Response

Unsaturated fatty acids protect beta-cells from the long-term negative effects of saturated fatty acids. The authors identified the mechanisms underlying this protective action of unsaturated fatty acids. Insulin-secreting MIN6 cells were exposed to palmitate in the absence or presence of oleate and analyzed by using nano-LC MS/MS based proteomic approach. [Biochim Biophys Acta] Abstract

Pancreatic β-Cell Production of CXCR3 Ligands Precedes Diabetes Onset

While the initial trigger that initiates the autoimmune process is unknown, there is a leukocytic infiltration that precedes islet β-cell death and dysfunction. The authors demonstrated that genes encoding the chemokines CXCL9, 10, and 11 are primary response genes in pancreatic β-cells and are also elevated as part of the inflammatory response in mouse, rat, and human islets. [Biofactors] Abstract

Quercetin Stimulates Insulin Secretion and Reduces the Viability of Rat INS-1 Beta-Cells

This study was performed to better understand short- and long-term effects of quercetin and rutin on beta-cells.Rutin, quercetin and the phosphoinositide-3-kinase inhibitor LY294002 caused a dose-dependent reduction in cell viability with IC50(subscript) values of ∼75 µM, ∼25 µM and ∼3.5 µM, respectively. [Cell Physiol Biochem] Full Article

Differential Influence of Tacrolimus and Sirolimus on Mitochondrial-Dependent Signaling for Apoptosis in Pancreatic Cells

Researchers examined and compared the mitochondria-related cellular mechanisms by which tacrolimus or sirolimus immunosuppressive drugs alter the pancreatic exocrine and endocrine β-cell fate. [Mol Cell Biochem] Abstract

PANCREATIC CANCER

Interaction of tRNA with MEK2 in Pancreatic Cancer Cells

Investigators tested the consequence of the interaction between tRNA and MEK2 in pancreatic cancer cell lines. They generated disease and drug resistance-derived MEK2 mutants to evaluate the function of the tRNA-MEK2 interaction. [Sci Rep] Full Article

Gestational Diabetes Mellitus: Does an Effective Prevention Strategy Exist?

The reviewers examine the evidence supporting lifestyle modification strategies in women with and without risk factors for gestational diabetes mellitus, and the efficacy of dietary supplementation and pharmacological approaches to prevent this disease. [Nat Rev Endocrinol] Abstract

Pharmacology and Therapeutic Implications of Current Drugs for Type 2 Diabetes Mellitus

The authors assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with type 2 diabetes mellitus within the context of disease pathogenesis and natural history. [Nat Rev Endocrinol] Abstract

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

ViaCyte to Present at ISSCR 2016 Annual Meeting

ViaCyte, Inc. announced a poster presentation on insulin-producing cells with characteristics of mature human beta cells originated within the Janssen BetaLogics group. [Press release from ViaCyte, Inc. discussing research presented at the 2016 International Society for Stem Cell Research (ISSCR) Annual Meeting, San Francisco] Press Release

BioLineRx Announces Regulatory Submissions for Phase IIa Trial of BL-8040 in Combination with KEYTRUDA^® (Pembrolizumab) for Treatment of Pancreatic Cancer

BioLineRx Ltd. announced the filing of regulatory submissions required to commence a Phase IIa trial for BL-8040 in combination with KEYTRUDA^® for the treatment of patients with pancreatic cancer. The study is expected to commence shortly after receipt of regulatory approval, anticipated in the third quarter of 2016. [BioLineRx Ltd.] Press Release

Akcea Announces Publication of Positive Volanesorsen Clinical Data Showing Reduced Triglycerides and Improved Insulin Sensitivity in Patients with High Triglycerides and Type 2 Diabetes

Akcea Therapeutics announced the publication in Diabetes Care of positive clinical data from a Phase II study of volanesorsen in patients with high plasma triglyceride (TG) levels and type 2 diabetes. Results from the study showed that, in addition to reductions in plasma TG and apolipoprotein C-III (ApoC-III), a key factor in TG regulation, volanesorsen improved insulin sensitivity and glucose control. [Echo Therapeutics, Inc.] Press Release

Researchers Reeling as UK Votes to Leave EU

The United Kingdom’s vote to leave the European Union has plunged it into political and economic uncertainty — and left researchers worried over the future of their funding and collaborations, the UK’s participation in major European research programs, and the freedom of movement and employment status of thousands of scientists. [Nature News] Editorial

NEW 2016 National Cancer Research Institute (NCRI) Cancer Conference
November 6-9, 2016
Liverpool, United Kingdom

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

NEW Principal Investigator – Tenure Track Position (National Institutes of Health)

NEW Postdoctoral Fellowship – Various Projects (University of Pittsburgh)

Research Fellow – Pancreatic β-Cell Biology and Regeneration (Dresden University of Technology)

Senior Lecturer – Pancreatic Cancer (Queen Mary University of London)

Postdoctoral Fellow – Pancreatic Cancer Metabolism (Thomas Jefferson University)

Postdoctoral Fellows – Various Positions (Oregon Health & Science University)

Senior Scientific Assistant – Pancreatic Ductal Adenocarcinoma (University of Cambridge)

PhD Studentship – Molecular and Translational Aspects of Pancreatic Cancer (German Cancer Research Center)

Postdoctoral Fellow – Quantitative Hepato-Pancreatic MR Imaging (Inserm)

Postdoctoral Fellow – Type 2 Diabetes and Insulin Resistance (King Abdullah University of Science and Technology)

PhD Studentship – Type 2 Diabetes and Insulin Resistance (King Abdullah University of Science and Technology)

Postdoctoral Fellow – Somatic Stem Cell Biology of Liver/Pancreas (The Swiss Federal Institute of Technology in Zurich)

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

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