Pancreatic Cell News Volume 4.00 | Jan 8 2013

DIABETES

Fetal PGC-1α Overexpression Programs Adult Pancreatic β-Cell Dysfunction
Scientists showed that glucocorticoids (GCs) stimulate the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a coregulator of the GCs receptor, and that the overexpression of PGC-1α represses genes important for β-cell development and function. [Diabetes] Abstract

G6PC2, A Negative Regulator of Basal Glucose-Stimulated Insulin Secretion
G6PC2 encodes an islet-specific, endoplasmic reticulum-resident glucose-6-phosphatase catalytic subunit. A combination of in situ perfused pancreas, in vitro isolated islet, and in vivo analyses were used to explore the function of G6pc2 in mice. [Diabetes] Abstract

Hydrogen Sulfide-Induced Inhibition of L-Type Ca²⁺ Channels and Insulin Secretion in Mouse Pancreatic Beta Cells
The whole-cell patch-clamp technique was used to record L-type voltage-dependent Ca²⁺ channels in beta cells from cystathionine γ-lyase-knockout and wild-type mice. Insulin secretion from pancreatic islets and endogenous H₂S production in pancreas were measured. [Diabetologia] Abstract

Selective Serotonin Reuptake Inhibitors (SSRIs) Inhibit Insulin Secretion and Action in Pancreatic Beta Cells
Investigators demonstrated that incubation of murine islets or Min6 β cell line with the SSRIs paroxetine, fluoxetine or sertraline inhibited insulin-induced Tyr phosphorylation of insulin receptor substrate-2 protein and the activation of its downstream targets Akt and S6K1. [J Biol Chem] Abstract | Full Article

Galectin-3 Deficiency Protects Pancreatic Islet Cells from Cytokine-Triggered Apoptosis In Vitro
The authors aimed to examine whether beta cell apoptosis depends on the presence of galectin-3 and to delineate the underlying mechanism. [J Cell Physiol] Abstract

PANCREATIC CANCER

Interaction of the Sympathetic Nerve with Pancreatic Cancer Cells Promotes Perineural Invasion through the Activation of STAT3 Signaling
Scientists used mouse dorsal root ganglia and pancreatic cancer cells co-cultured in vitro, cellular and molecular biology and animal models to evaluate the function of the sympathetic neurotransmitter norepinephrine in perineural invasion progression and pathogenesis. [Mol Cancer Ther] Abstract

Targeted Degradation of KRAS by an Engineered Ubiquitin Ligase Suppresses Pancreatic Cancer Cell Growth In Vitro and In Vivo
Interactions between RC-U, an engineered E3 ubiquitin ligase, and KRAS as well as whether RC-U could ubiquitinate KRAS were investigated. Extracellular signal-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK 1/2 levels were examined in pancreatic cancer cells transfected with plasmid RC-U. [Mol Cancer Ther] Abstract

Downregulation of TRAF2 Mediates NIK-Induced Pancreatic Cancer Cell Proliferation and Tumorigenicity
Researchers identified proteasomal downregulation of TNF receptor-associated factor 2 (TRAF2) as a mechanism by which levels of active NF-κB-inducing kinase (NIK) are increased in pancreatic ductal adenocarcinoma cell lines. [PLoS One] Full Article | Press Release

MUC5AC Protects Pancreatic Cancer Cells from TNF-Related Apoptosis-Inducing Ligand-Induced Death Pathways
The authors previously reported that a specific siRNA transfected MUC5AC could knockdown MUC5AC expression and suppress in vivo tumor growth and metastasis, although it had no effects on in vitro cell growth, cell survival, proliferation and morphology. Here, they investigated which host immune cells induced these effects and how the effects were induced using immunocyte-depleted animal models. [Int J Oncol] Abstract

EZH2 Is Required for Breast and Pancreatic Cancer Stem Cell Maintenance and Can Be Used as a Functional Cancer Stem Cell Reporter
Researchers hypothesized that epigenetic modification by EZH2 helps maintain the cancer stem cell (CSC) phenotype and that in turn this epigenetic modifier can be used as a reporter for CSC activity in an in vitro high-throughput screening assay. CSCs isolated from pancreatic and breast cancer lines had elevated EZH2 levels over non-CSCs. [Stem Cells Transl Med] Abstract

REVIEWS

Coming Full Circle in Diabetes Mellitus: From Complications to Initiation
The authors examined how the development of diabetes mellitus has come full circle from initiation to complications and suggests that the development of diabetes mellitus and the progression to chronic complications both require the same mechanistic triggers. [Nat Rev Endocrinol] Abstract

Immune Therapy in Type 1 Diabetes Mellitus
Although long-term preservation of β-cell function has been difficult to achieve in many studies, considerable progress is being made through controlled clinical trials and animal investigations towards uncovering mechanisms of β-cell destruction. [Nat Rev Endocrinol] Abstract

Zinc, Pancreatic Islet Cell Function and Diabetes: New Insights into an Old Story
The author summarizes the effects of zinc (Zn) on pancreatic β-cell function, including insulin synthesis and secretion, Zn signaling in the pancreatic islet, the redox functions of Zn and its target genes. [Nutr Res Rev] Abstract

Esperion Announces Positive Topline Results from a Phase II Clinical Trial of ETC-1002 in Patients with Type 2 Diabetes
Esperion Therapeutics announced positive results of a recently completed phase II clinical trial of ETC-1002 in patients with type 2 diabetes with LDL-C lowering of up to 43% compared to placebo. [Esperion Therapeutics, Inc.] Press Release

Lilly Reassumes Sole Worldwide Development and Commercialization Rights for Novel Basal Insulin Analog
Eli Lilly and Company and Boehringer Ingelheim International GmbH announced they will adjust the scope of their diabetes alliance with respect to LY2605541, Lilly’s investigational novel basal insulin analog, with Lilly reassuming sole worldwide development and commercialization rights to LY2605541. [Eli Lilly and Company] Press Release

NGM Enters Agreement with Janssen to Discover and Develop Novel Therapeutics for Diabetes
NGM Biopharmaceuticals, Inc. announced that it has signed a worldwide agreement with Janssen Pharmaceuticals, Inc. to discover and develop novel therapeutics for the potential treatment of Type 2 diabetes and other metabolic diseases. [NGM Biopharmaceuticals, Inc.] Press Release

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National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW The Jackson Laboratory: How to Select and Maintain Mouse Models of Type 1 Diabetes
January 10, 1:00PM (ET in US)
Webinar

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Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc.)

MSc – Future Opportunities (STEMCELL Technologies, Inc.)

PhD – Future Opportunities (STEMCELL Technologies, Inc.)

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

Postdoctoral Position – Pancreatic/Liver Cell Differentiation in Development and Cancer (de Duve Institute)

Postdoctoral Position – Diabetes and Beta-Cell Regeneration in Mice (Karolinska Institute)

Postdoctoral Researcher (The University of Texas Health Science Center at San Antonio)

Postdoctoral Fellow – Pancreatic Beta Cell Biology (CeMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences)

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