Pancreatic Cell News Volume 3.38 | Sep 25 2012

Divalent Metal Transporter 1 Regulates Iron-Mediated ROS and Pancreatic β Cell Fate in Response to Cytokines
Reactive oxygen species (ROS) contribute to target-cell damage in inflammatory and iron-overload diseases. Through a combination of in vitro and in vivo studies, researchers showed that the proinflammatory cytokine IL-1β induces divalent metal transporter 1 expression correlating with increased β cell iron content and ROS production. [Cell Metab] Abstract | Press Release | Graphical Abstract

DIABETES

Wolfram Syndrome 1 and Adenylyl Cyclase 8 Interact at the Plasma Membrane to Regulate Insulin Production and Secretion
Researchers provide evidence that wolfram syndrome 1 (WFS1) is essential for glucose- and glucagon-like peptide 1-stimulated cyclic AMP production and regulation of insulin biosynthesis and secretion. Stimulation with glucose causes WFS1 translocation from the endoplasmic reticulum to the plasma membrane, where it forms a complex with adenylyl cyclase 8. [Nat Cell Bio] Abstract

CXCR1/2 Inhibition Enhances Pancreatic Islet Survival after Transplantation
The authors found that CXCR1/2 chemokine receptors and their ligands are crucial negative determinants for islet survival after transplantation. Pancreatic islets released abundant CXCR1/2 ligands (CXCL1 and CXCL8). Accordingly, intrahepatic CXCL1 and circulating CXCL1 and CXCL8 were strongly induced shortly after islet infusion. [J Clin Invest] Full Article

Abnormal Endocrine Pancreas Function at Birth in Cystic Fibrosis Ferrets
The lack of an animal model for cystic fibrosis (CF)-related diabetes (CFRD) has made it difficult to dissect how the onset of pancreatic pathology influences the emergence of CFRD. Scientists evaluated the structure and function of the neonatal CF endocrine pancreas using a new CF transmembrane conductance regulator-knockout ferret model. [J Clin Invest] Full Article | Press Release

Nonviral Delivery of Small Interfering RNA Into Pancreas-Associated Immune Cells Prevents Autoimmune Diabetes
It was found that lipid- or polyethylenimine-based delivery agents were efficient to address small interfering RNA molecules within pancreas-associated antigen-presenting cells, but not β-cells, and particularly a CD11b⁺ cell population comprising both CD11b⁺CD11c^neg macrophages and CD11b⁺CD11c⁺ dendritic cells. [Mol Ther] Abstract

¹¹C-Hydroxytryptophan Uptake and Metabolism in Endocrine and Exocrine Pancreas
Determination of the residual β-cell mass using noninvasive tools might help to follow up the efficacy of new treatments in both type 1 and type 2 diabetes mellitus, including islet transplantation. Investigators evaluated the uptake mechanism and the retention of the PET tracer ¹¹C-hydroxytryptophan in endocrine and exocrine pancreas in vitro and in vivo. [J Nucl Med] Abstract

PANCREATIC CANCERR

CXCL12/CXCR4 Signaling Axis Induces SHH Expression in Pancreatic Cancer Cells via ERK- and Akt- Mediated Activation of NF-κB: Implications for Bidirectional Tumor-Stromal Interactions
Scientists demonstrated that CXCL12 leads to a dose- and time-dependent upregulation of sonic hedgehog (SHH) in pancreatic cancer cells. CXCL12-induced SHH upregulation is specifically mediated through the receptor CXCR4 and is dependent on the activation of downstream Akt and extracellular regulated kinase (ERK) signaling pathways. [J Biol Chem] Abstract | Full Article

Unlike Pancreatic Cancer Cells Pancreatic Cancer Associated Fibroblasts Display Minimal Gene Induction after 5-Aza-2′-Deoxycytidine
Aberrant DNA methylation is an important cause of transcriptional alterations in cancer cells but it is not known how important DNA methylation alterations are to cancer associated stromal fibroblasts behavior. Scientists used Affymetrix exon arrays to compare genes induced by the DNA methylation inhibitor 5-aza-dC in cultured pancreatic cancer associated fibroblasts, pancreatic control fibroblasts and pancreatic cancer cell lines. [PLoS One] Full Article

Validation of Polo-Like Kinase 1 as a Therapeutic Target in Pancreatic Cancer Cells
The authors showed that the expression level of polo-like kinase 1 (PLK1) is upregulated in human pancreatic cancer cells. Molecular modeling studies indicate that DMTC inhibits PLK1 activity through competitive displacement of ATP from its binding pocket. [Cancer Biol Ther] Abstract

Inhibition of Cell Proliferation by a Selective Inhibitor of the Ca²⁺-Activated Cl⁻ Channel, Ano1
Researchers investigated the effect of the T16A_inh-A01 inhibitor on proliferation in interstitial cells of Cajal and in the Ano1-expressing human pancreatic cancer cell line CFPAC-1. [Biochem Biophys Res Commun] Abstract

REVIEWS

The Role of Adipokines in Beta-Cell Failure of Type 2 Diabetes
This review discusses the published evidence for the role of individual adipokines on the function, proliferation, death and failure of beta-cells, focusing on adipokines reported to have the most significant effects. [J Endocrinol] Abstract | Full Article

Role of Inflammatory Mechanisms in Pathogenesis of Type 2 Diabetes Mellitus
This review focuses on the recent advances in progression of type 2 diabetes mellitus including various inflammatory mechanisms that might induce inflammation, insulin resistance, decrease insulin secretion from pancreatic islets and dysfunctioning of β-cells. [J Cell Biochem] Abstract

Threshold Pharmaceuticals to Present Updated Data from Phase IIb Clinical Trial of TH-302 in Combination with Gemcitabine in Advanced Pancreatic Cancer
Threshold Pharmaceuticals, Inc. announced that data from a randomized open-label phase IIb clinical trial of investigational hypoxia-targeted drug TH-302 in patients with advanced pancreatic cancer, will be presented. [Press release from Threshold Pharmaceuticals, Inc. discussing data to be presented at European Society for Medical Oncology 2012 Congress (ESMO), Vienna] Press Release

Biodel Awarded NIH Grant to Develop Glucagon Formulations for Use in Artificial Pancreas
Biodel Inc. announced that the Small Business Innovation Research program of the National Institutes of Health (NIH) has awarded Biodel a grant for the development of novel and stable glucagon formulations for use in an artificial pancreas, also known as a closed loop pump system. [Biodel Inc.] Press Release

JDRF Announces Winners of the Theoretical Phase of Its Agnes Varis Glucose-Responsive Insulin Grand Challenge Prize
JDRF, the leading global organization focused on type 1 diabetes research, announced the winners of the Theoretical Phase of its first-ever public challenge, which called for novel theoretical ideas to approach the discovery and development of glucose-responsive insulin to treat diabetes. [JDRF] Press Release

Baxter and Onconova Announce European Licensing Agreement for Anti-Cancer Compound Rigosertib
Baxter International Inc. and Onconova Therapeutics, Inc. announced that they have entered into a European licensing agreement for rigosertib, a novel targeted anti-cancer compound currently in a phase III study for the treatment of a group of rare hematologic malignancies called myelodysplastic syndromes and in a phase II/III study for pancreatic cancer. [Onconova Therapeutics, Inc.] Press Release

IntelliCell BioSciences Announces Clinical Study for Diabetic Critical Limb Ischemia
IntelliCell BioSciences, Inc. announced that it will be initiating an in-human clinical study to treat people who suffer from diabetic induced critical limb ischemia wounds.  IntelliCell has developed a proprietary treatment methodology using its autologous cellular therapy that includes adult stem cells that have demonstrated regenerative capabilities in anecdotal studies of patients treated. [PR Newswire Association LLC]
Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)
 
Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW BIT’s 3^rd Annual World Congress of Molecular & Cell Biology
June 14-16, 2013
Suzhou, China

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

Research Technologist – Media Development (STEMCELL Technologies, Inc.)

Research Technologist – Research and Development (STEMCELL Technologies, Inc.)

Quality Control Operations Coordinator (STEMCELL Technologies, Inc.)

Scientific Communications & Publishing Coordinator (STEMCELL Technologies, Inc.)

Product Manager – Hematopoietic (STEMCELL Technologies, Inc.)

Clinical Investigator – Biomedical Research Program (Weill Cornell Medical College)

Postdoctoral Position – Type 2 Diabetic Human Induced Pluripotent Stem Modeling (University of Lille Nord de France)

Postdoctoral Position – Cancer Therapeutics (Massachusetts General Hospital)

Postdoctoral Position – Dysfunction in Diabetes (University of Oxford)

Postdoctoral Position – Beta Cell Biology and Translational Research (University of California, Los Angeles)

Postdoctoral Position – Cancer Therapeutics in Pancreatic Cancer (Harvard Medical School)

Recruit Top Talent: Reach more than 55,000 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? Email info@connexoncreative.com with your feedback.