Pancreatic Cell News Volume 6.07 | Feb 24 2015

Insulin Secretory Granules Control Autophagy in Pancreatic β Cells
In contrast to many mammalian cells, macroautophagy in pancreatic β cells was suppressed upon starvation. Starved β cells induced lysosomal degradation of nascent secretory insulin granules, which was controlled by protein kinase D, a key player in secretory granule biogenesis. [Science] Abstract

Feedback Inhibition of CREB Signaling Promotes Beta Cell Dysfunction in Insulin Resistance
Scientists showed that mice with a knockout of the CREB coactivator CRTC2 in beta cells have impaired oral glucose tolerance due to decreases in circulating insulin concentrations. CRTC2 was found to promote beta cell function in part by stimulating the expression of the transcription factor MafA. [Cell Rep]
Full Article | Graphical Abstract

Alginate Encapsulant Incorporating CXCL12 Supports Long-Term Allo- and Xenoislet Transplantation without Systemic Immune Suppression
Researchers investigated the effect of alginate microcapsules incorporating CXCL12 on islet function. Coating of islets with CXCL12 or microencapsulation of islets with alginate incorporating the chemokine, resulted in long-term allo- and xenoislet survival and function, as well as a selective increase in intragraft regulatory T cells. [Am J Transplant] Abstract | Press Release

Ets-1 as an Early Response Gene against Hypoxia-Induced Apoptosis in Pancreatic β-Cells
Scientists identified the transcription factor Ets-1 (v-ets erythroblastosis virus E26 oncogene homolog 1) as an early response gene against hypoxia-induced apoptosis in pancreatic β-cells. [Cell Death Dis] Full Article

Compensatory Hyperinsulinemia in High-Fat Diet-Induced Obese Mice Is Associated with Enhanced Insulin Translation in Islets
Scientists investigated whether insulin synthesis was altered in correlation with a high-fat diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. [Biochem Biophys Res Commun] Abstract

PANCREATIC CANCER

Antitumor Effect of Anti-Tissue Factor Antibody-MMAE Conjugate in Human Pancreatic Tumor Xenografts
Researchers investigated the anti-tumor effect of an antibody-drug conjugate (ADC) consisting of an anti-tissue factor monoclonal antibody and monomethyl auristatin E (MMAE). The cytotoxic and antitumor effects of the ADCs against four pancreatic cancer cell lines were analyzed. [Int J Cancer] Abstract | Full Article

Tenascin-C Induces Resistance to Apoptosis in Pancreatic Cancer Cells through Activation of ERK/NF-κB Pathway
Scientists performed an analysis to determine the effects of tenascin-C on modulating cell apoptosis and chemo-resistance and explored its mechanisms involving activation in pancreatic cancer cells. [Apoptosis] Abstract

Hexon Modification to Improve the Activity of Oncolytic Adenovirus Vectors against Neoplastic and Stromal Cells in Pancreatic Cancer
Scientists inserted the TGFβ receptor targeting peptide CKS17 into the hypervariable region 5 of the capsid protein hexon with the aim to generate a replicating Ad vector with improved activity in complex tumors. They demonstrated increased transduction of both pancreatic cancer cell lines and of pancreatic stellate cells and enhanced cytotoxicity in co-cultures of both cell types. [PLoS One] Full Article

The Epigenetic Agents Suberoylanilide Hydroxamic Acid and 5-AZA-2′ Deoxycytidine Decrease Cell Proliferation, Induce Cell Death and Delay the Growth of MiaPaCa2 Pancreatic Cancer Cells In Vivo
Treatment with histone deacetylase inhibitors and DNA methyltransferase inhibitors decreased cell proliferation in MiaPaCa2 cells, and suberoylanilide hydroxamic acid treatment, with or without 5-AZA-2′ deoxycytidine (5-AZA-dc), resulted in higher cell death and lower DNA synthesis compared to 5-AZA-dc alone and controls. [Int J Oncol] Abstract

Oncogenic miR-23a in Pancreatic Ductal Adenocarcinogenesis via Inhibiting APAF1
Ectopic miR-23a significantly suppressed the APAF1 gene expression in pancreatic cancer cells. Similar to siAPAF1, miR-23a significantly promoted pancreatic cancer cell proliferation and repressed apoptosis. [Dig Dis Sci] Abstract

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ABRAXANE^® Now Reimbursed in Italy as a First-Line Treatment of Adult Patients with Metastatic Pancreatic Cancer
Celgene International Sàrl announced that Italian authorities have issued a positive decision for NHS reimbursement of ABRAXANE^® in combination with gemcitabine, for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, or pancreatic cancer. [Celgene International Sàrl (Business Wire)] Press Release

Lilly Announces Update on Regulatory Submission Timing for Basal Insulin Peglispro
Eli Lilly and Company announced a delay in the submission of basal insulin peglispro to regulatory agencies beyond the first quarter of 2015. The delay includes filings with the U.S. Food and Drug Administration and the European Medicines Agency. [Eli Lilly and Company] Press Release

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)

Therapeutic Goods Administration (Australia)

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

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Position – Endothelial Dysfunction and Diabetes (Weill Cornell Medical College in Qatar)

Director – Vector Production (Sangamo BioSciences, Inc.)

Senior Process Development Engineer (Sangamo BioSciences, Inc.)

Assistant/Associate Professor – Endocrinology, Diabetes and Metabolism Research (University of Pennsylvania)

PhD Scholarships – Diabetes (Danish Diabetes Academy)

Postdoctoral Fellow – Wnt Signaling in Development and Disease (Van Andel Research Institute)

Postdoctoral Research Fellow – Post-Transcriptional Gene Regulation Governing Cancer Cell Behavior (Fred Hutchinson Cancer Research Center)

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