Pancreatic Cell News Volume 4.47 | Dec 3 2013

Intermittent Hypoxia Exacerbates Pancreatic β-Cell Dysfunction in a Mouse Model of Diabetes Mellitus
Scientists hypothesized that intermittent hypoxia would exacerbate pancreatic β-cell dysfunction and alter the fatty acids in the male Tallyho/JngJ mouse, a rodent model of type 2 diabetes. Ex vivo exposure of pancreatic islets to palmitic acid suppressed insulin secretion and decreased islet cell viability. [Sleep] Abstract

GATA Factors Promote ER Integrity, β-Cell Survival, and Contribute to Type 1 Diabetes Risk
To investigate the role of GATA factors in adult β-cells, researchers derived β-cell inducible Gata4 and Gata6 knockout mice, along with whole-body inducible Gata4 knockouts. β-cell Gata4 deletion modestly increased the proportion of dying β-cells in situ with ultrastructural abnormalities suggesting endoplasmic reticulum (ER) stress. [Mol Endocrinol] Abstract

Gastric Bypass Surgery May Improve Beta Cell Apoptosis with Ghrelin Overexpression in Patients with BMI ≥ 32.5 kg/m²
To determine the effect of ghrelin on inhibition of apoptosis, INS-1 cells were cultured in a high glucose concentration and treated with acylated ghrelin (AG), unacylated ghrelin (UAG), or obestatin (OB). Treatment with AG, UAG, and OB inhibited intracellular calcium mobilization and intramitochondrial calcium accumulation in INS-1 cells to protect the cells from hyperglycemia-induced apoptosis. [Obes Surg] Abstract

Generation of Insulin-Producing Cells from Rat Mesenchymal Stem Cells Using an Aminopyrrole Derivative XW4.4
In vitro studies indicated that treatment of rat mesenchymal stem cells with compound XW4.4 resulted in differentiated cells with characteristics of insulin producing cells including islet-like clusters, spherical, grape-like morphology, insulin secretion, positive for dithizone, glucose stimulation and expression of pancreatic endocrine cell marker genes. [Chem Biol Interact] Abstract

Generation of Functional Insulin-Producing Cells From Mouse Embryonic Stem Cells through 804G Cell-Derived Extracellular Matrix and Protein Transduction of Transcription Factors
Researchers established an effective method of differentiation through the protein transduction of three transcription factors important to pancreatic β cell development. Transduction of the three proteins induced the differentiation of mouse embryonic stem and mouse induced pluripotent stem cells into insulin-producing cells. [Stem Cells Transl Med] Abstract

PANCREATIC CANCER

Combined Inhibition of Notch and JAK/STAT Is Superior to Monotherapies and Impairs Pancreatic Cancer Progression
Researchers assessed the combinational effects of the γ-secretase inhibitor IX (GSI IX) and JAK2 inhibitor (AG-490) on growth and epithelial plasticity of human pancreatic cancer cell lines, and in a genetically engineered mouse model of pancreatic ductal adenocarcinoma. Dual treatment with GSI IX and AG-490 significantly impaired cell proliferation, migration, invasion, soft agar growth and apoptosis when compared to monotherapies. [Carcinogenesis] Abstract

Selective Inhibition of Pancreatic Ductal Adenocarcinoma Cell Growth by the Mitotic MPS1 Kinase Inhibitor, NMS-P715
Scientists showed that the degree of up-regulation in 70 chromosome instability genes (CIN70) varies considerably among pancreatic ductal adenocarcinoma tumors, with higher CIN70 gene expression predictive of poor outcome. They identified a 25 gene subset whose over-expression was most strongly correlated with poor survival and included MPS1. [Mol Cancer Ther] Abstract

Phospho-Sulindac Inhibits Pancreatic Cancer Growth: NFATc1 as a Drug Resistance Candidate
The role of increased nuclear factor of activated T-cells, isoform c1 (NFATc1) expression on the growth inhibitory effect of phospho-sulindac (P-S) on cancer growth was evaluated by silencing or by overexpressing it both in vitro and in vivo. Scientists found that when the expression of NFATc1 was abrogated by RNAi, pancreatic cancer cells were more responsive to treatment with P-S. [Int J Oncol] Abstract

hsa-miR-141 Downregulates TM4SF1 to Inhibit Pancreatic Cancer Cell Invasion and Migration
Researchers aimed to identify and characterize microRNAs that regulate transmembrane-4-L-six-family-1 (TM4SF1) expression in PC cells. The miR-141 levels negatively correlated with the TM4SF1 protein levels in PC cells. [Int J Oncol] Abstract

Escin Chemosensitizes Human Pancreatic Cancer Cells and Inhibits the Nuclear Factor-KappaB Signaling Pathway
Researchers evaluated the effect of Escin alone and combined with chemotherapy on pancreatic cancer cell survival and to unravel mechanism(s) of Escin anticancer activity. Escin decreased the survival of pancreatic cancer cells. [Biochem Res Int] Abstract

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Sanofi Announces New Phase III Results for Investigational New Insulin U300
Sanofi announced the full results from the EDITION II study showing that investigational new insulin U300 demonstrated similar blood sugar control with 23% fewer patients experiencing night-time low blood sugar compared with Lantus®. [Press release from Sanofi discussing research presented at the 2013 World Diabetes Congress, Melbourne] Press Release

Ryzodeg® Offers Improved Glycemic Control with Significantly Lower Rates of Hypoglycemia Compared to Biphasic Insulin Aspart 30 in Adults with Type 2 Diabetes
Data showed that adults with type 2 diabetes achieved improved glycemic control, significantly lower rates of overall and nocturnal confirmed hypoglycemia for the full trial period, and a significantly lower rate of severe hypoglycemia during the maintenance period with Ryzodeg® compared to biphasic insulin aspart 30, both administered twice-daily. [Press release from Novo Nordisk A/S discussing research presented at the 2013 World Diabetes Congress, Melbourne] Press Release

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Maryland Stem Cell Research Commission Presents Sixth Annual Maryland Stem Cell Research Symposium in Baltimore
Each year, the State of Maryland continues to lead advancements and best practices in U.S. stem cell research through the Maryland Stem Cell Research Fund. To celebrate and share the most current research coming out of the state, more than 350 scientists, researchers, bioethicists, patient advocates, government officials and members of the public came together to attend the Sixth Annual Maryland Stem Cell Research Symposium at Johns Hopkins University School of Medicine Campus in Baltimore. [PRNewswire Association LLC] Press Release

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Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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

NEW Chief Medical Officer – Novel Therapeutics in Oncology and Autoimmune Disease (Immunomedics, Inc.)

NEW Physician – Diabetes Clinical Research (Eli Lilly)

NEW Postdoctoral Fellowship – Novel Beta Cell Biomarkers (Université Libre de Bruxelles)

NEW Cancer Research UK Cambridge Institute PhD Studentships (University of Cambridge)

Faculty Fellowship – Diabetes Research (Joslin Diabetes Center)

Postdoctoral Position – Pancreatic Cancer Research (The University of Texas Health Science Center at San Antonio)

Faculty Position – Department of Cellular & Structural Biology (The University of Texas Health Science Center at San Antonio)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

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