Pancreatic Cell News Volume 4.38 | Oct 1 2013

Intraislet SLIT-ROBO Signaling Is Required for Beta-Cell Survival and Potentiates Insulin Secretion
Scientists found SLIT1 and SLIT3 in both beta cells and alpha cells, whereas SLIT2 was predominantly expressed in beta cells. Slit-Roundabout receptor (ROBO)1 and ROBO2 receptors were detected in beta and alpha cells. Remarkably, even modest knockdown of Slit production resulted in significant beta-cell death, demonstrating a critical autocrine/paracrine survival role for this pathway. [Proc Natl Acad Sci USA] Abstract

SMAD2 Disruption in Mouse Pancreatic Beta Cells Leads to Islet Hyperplasia and Impaired Insulin Secretion Due to the Attenuation of ATP-Sensitive K⁺ Channel Activity
To identify distinct roles for the downstream components of the canonical TGF-β signaling pathway, a Cre-loxP system was used to disrupt SMAD2, an intracellular transducer of TGF-β signals, in pancreatic beta cells. [Diabetologia] Abstract

Defective Prolactin Signaling Impairs Pancreatic Beta Cell Development during the Perinatal Period
Researchers provide evidence that expansion of beta cell mass during both embryogenesis and the postnatal period is impaired in the prolactin receptor-/- mouse model. [Am J Physiol Endocrinol Metab] Abstract

Reprogramming of Pig Dermal Fibroblast into Insulin Secreting Cells by a Brief Exposure to 5-Aza-Cytidine
Pig dermal fibroblasts were exposed to DNA methyltransferase inhibitor 5-aza-cytidine for 18 hours. After a brief recovery period, fibroblasts were subjected to a three-step protocol for the induction of endocrine pancreatic differentiation that was completed after 42 days. [Stem Cells Rev] Abstract

PANCREATIC CANCER

Epithelial Splicing Regulatory Protein 1 Is a Favorable Prognostic Factor in Pancreatic Cancer that Attenuates Pancreatic Metastases
Increased epithelial splicing regulatory protein 1 (ESRP1) expression was associated with longer survival in comparison with low ESRP1 expression, and PANC-1 cells engineered to express ESRP1 exhibited increased FGFR-2 IIIb expression and decreased migration and invasion in vitro, whereas ESRP1 small interference RNA-transfected KLM-1 cells exhibited increased FGFR-2 IIIc expression and increased cell growth, migration and invasion. [Oncogene] Abstract

The Neurotrophic Factor Neurturin Contributes towards an Aggressive Cancer Cell Phenotype, Neuropathic Pain and Neuronal Plasticity in Pancreatic Cancer
The impact of neurotrophic factor neurturin (NRTN)/GFRα-2 on pancreatic cancer (PCa) cell (PCC) biology was investigated via exposure to hypoxia, MTT viability and Matrigel invasion assays in native and specific siRNA-silenced PCCs. PCa tissue and PCCs contained increased amounts of NRTN, which was suppressed under hypoxia. [Carcinogenesis] Abstract

Targeting Pancreatic Cancer with Magneto-Fluorescent Theranostic Gold Nanoshells
Researchers report a magneto-fluorescent theranostic nanocomplex targeted to neutrophil gelatinase-associated lipocalin (NGAL) for imaging and therapy of pancreatic cancer. Anti-NGAL-conjugated theranostic gold nanoshells specifically targeted pancreatic cancer cells in vitro and in vivo providing contrast for both near-infrared fluorescence and T₂-weighted MRI with higher tumor contrast than can be obtained using long-circulating, but nontargeted, PEGylated nanoparticles. [Nanomedicine] Abstract

A Binuclear Complex Constituted by Diethyldithiocarbamate and Copper(I) Functions as a Proteasome Activity Inhibitor in Pancreatic Cancer Cultures and Xenografts
Researchers investigated the anticancer potential of this complex on pancreatic cancer and the possible mechanism. The results suggest that diethyldithiocarbamate-Cu(I) inhibit pancreatic cancer cell proliferation and proteasome activity in vitro and in vivo. [Toxicol Appl Pharmacol] Full Article

Lysophosphatidic Acid Stimulates Activation of Focal Adhesion Kinase and Paxillin and Promotes Cell Motility, via LPA1-3, in Human Pancreatic Cancer
Researchers examined the involvement of lysophosphatidic acid (LPA)1-3 in LPA-induced activation of focal adhesion kinase and paxillin, and in cell motility, in pancreatic cancer PANC-1 cells. Three LPA receptors were significantly expressed in PANC-1 cells. [Dig Dis Sci] Abstract

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Leading Pharma Company Selects Clinilabs to Conduct a Phase I Study of an Investigational Type 2 Diabetes Medication
Clinilabs, a contract research organization that provides early-stage and specialty clinical drug development services to industry, announced that they have begun a Phase I clinical research study of an investigational medication for Type 2 Diabetes Mellitus. [Clinilabs Inc.] Press Release

JDRF Honors Researchers Whose Insights on Early Type 1 Diabetes Development Have Set the Stage for Disease Prevention in Children
JDRF awarded three talented scientists its prestigious Mary Tyler Moore and S. Robert Levine, M.D., Excellence in Clinical Research Award, recognizing their important contributions toward understanding the natural history and pathogenesis of type 1 diabetes in children. [JDRF] Press Release

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Postdoctoral Position – Cardiovascular Development and Diabetes (Cornell University)

Postdoctoral Researcher – Molecular Mechanisms of Innate Immunity and Inflammation (University of North Carolina at Chapel Hill)

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Postdoctoral Position – Mechanism of Pancreatic Beta Cell Proliferation (Joslin Diabetes Center/Harvard Medical School)

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