Pancreatic Cell News Volume 3.47 | Nov 27 2012

DIABETES

Lysine 63-Linked Ubiquitination Modulates Mixed Lineage Kinase-3 Interaction with JIP1 Scaffold protein in Cytokine-Induced Pancreatic Beta Cell Death
In an effort to identify mechanisms that regulate mixed lineage kinase-3 (MLK3) activity in beta cells, scientists discovered that IL-1β stimulates lysine 63-linked ubiquitination of MLK3 via a conserved, TRAF6-binding peptapeptide motif in the catalytic domain of the kinase. [J Biol Chem] Abstract | Full Article

Susceptibility to Fatty Acid-Induced β-Cell Dysfunction Is Enhanced in Prediabetic Diabetes-Prone BioBreeding Rats: A Potential Link between β-Cell Lipotoxicity and Islet Inflammation
The authors examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding rat, its diabetes-resistant BioBreeding control, and normal Wistar-Furth rats. [Endocrinology] Abstract

N-Acyl Taurines Trigger Insulin Secretion by Increasing Calcium Flux in Pancreatic β-Cells
Researchers discovered that treatment of pancreatic β-cell lines and rat islet cell lines with N-acyl taurines induced a high frequency of calcium oscillations in these cells. [Biochem Biophys Res Commun] Abstract

Inhibition of Insulin Secretion from Rat Pancreatic Islets by Dexmedetomidine and Medetomidine, Two Sedatives Frequently Used in Clinical Settings
Investigators aimed to determine whether dexmedetomidine and medetomidine, α₂-adrenergic agonists clinically used as sedatives, influence insulin secretion from rat pancreatic islets. [Endocr J] Abstract

Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis
Investigators showed that progenitor cells forming the ducts of the embryonic pancreas express planar cell polarity (PCP) proteins and exhibit an active PCP pathway. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. [Cell Rep] Full Article | Graphical Abstract

PANCREATIC CANCER

MiR-148b Functions as a Tumor Suppressor in Pancreatic Cancer by Targeting AMPKα1
Studies revealed that AMPKα1 might be the direct target gene of microRNA (miR)-148b, and overexpressed AMPKα1 inversely correlated with miR-148b in pancreatic cancer. Silencing of AMPKα1 with RNAi inhibited the growth of pancreatic cancer cells in vitro and in vivo, and also induced apoptosis, cell cycle arrest and inhibited invasion of cancer cells, which is consistent with the effects of miR-148b overexpression. [Mol Cancer Ther] Abstract

Monogalactosyl Diacylglycerol, a Replicative DNA Polymerase Inhibitor, from Spinach Enhances the Anti-Cell Proliferation Effect of Gemcitabine in Human Pancreatic Cancer Cells
Scientists discovered that in cell growth suppression by gemcitabine (GEM), pre-addition of monogalactosyl diacylglycerol (MGDG) significantly enhanced cell proliferation suppression, and the combination of these compounds was found to induce apoptosis. In contrast, GEM-treated cells followed by MGDG addition did not influence cell growth. [Biochim Biophys Acta] Abstract

Cucurmosin Kills Human Pancreatic Cancer SW-1990 Cells In Vitro and In Vivo
The authors investigated the effect of cucurmosin on proliferation inhibition in the human pancreatic cancer cell line SW-1990 in vitro and in vivo. [Anticancer Agents Med Chem] Abstract

Metformin Inhibition of mTORC1 Activation, DNA Synthesis and Proliferation in Pancreatic Cancer Cells: Dependence on Glucose Concentration and Role of AMPK
Researchers demonstrated that the potency of metformin induced AMPK activation was dramatically enhanced in human pancreatic ductal adenocarcinoma cells PANC-1 and MiaPaCa-2 cultured in medium containing physiological concentrations of glucose (5 mM), as compared with parallel cultures in medium with glucose at 25 mM. [Biochem Biophys Res Commun] Abstract

REVIEWS

Tiltan Pharma Announces Enrollment of First U.S. Patient in a Phase II Clinical Trial of TL-118, Anti-Angiogenic Treatment for Metastatic Pancreatic Cancer
Tiltan Pharma Ltd. announced that it has enrolled the first U.S. patient in a phase II clinical trial of its anti-angiogenic product, TL-118, for the treatment of metastatic pancreatic cancer. The clinical trial will enroll 80 patients with newly diagnosed metastatic pancreatic cancer that have not yet been treated with chemotherapy. [Tiltan Pharma Ltd.] Press Release

Rhythm Expands Series B Financing to $33 Million; Adds Pfizer Ventures as an Investor
Rhythm announced that the company has raised an additional $8 million to complete a $33 million Series B financing. The additional $8 million comes from new investor, Pfizer Venture Investments. Rhythm will use the proceeds to further develop its small-peptide therapeutics for metabolic diseases. RM-131 is a ghrelin agonist currently in phase II clinical trials for diabetic gastroparesis and GI functional disorders. RM-493 is a melanocortin 4 receptor agonist that is completing phase I clinical trials for the treatment of obesity and diabetes. [Rhythm Pharmaceuticals] Press Release

MabVax Therapeutics Closes $5.25 Million Financing with Numoda Capital Innovations, Burrill Capital Fund IV, and RTP Venture Fund
MabVax Therapeutics, Inc. announced the closing of the first tranche in their Series B financing. Numoda Capital Innovations led the round and was joined by existing investors Burrill Capital Fund IV and RTP Venture Fund for an aggregate investment of $5.25 million. The additional capital will allow MabVax to continue the development of its phase II vaccine aimed at preventing recurrent sarcoma and its 5B1 antibody program targeting metastatic pancreatic cancer. [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)

Research Technologist – Cell Separation (STEMCELL Technologies, Inc.)

Product Quality Scientist (STEMCELL Technologies, Inc.)

Scientist – Endothelial Cell Research (STEMCELL Technologies, Inc.)

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

Quality Control Analyst (STEMCELL Technologies, Inc.)

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

Postdoctoral Position – Tumor Stem Cells (Cancer Institute of New Jersey)

Postdoctoral Fellow – Beta-Cell Regeneration in Zebrafish (Karolinska Institute, Cell and Molecular Biology)

Postdoctoral Position – Beta Cell Biology (Sanford Health/University of South Dakota)

Postdoctoral Position – In Vivo Drug Discovery Using Zebrafish (Karolinska Institute)

Postdoctoral Position – Novel Receptors in Endocrine Pancreas Development (TU-Dresden)

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