Pancreatic Cell News Volume 8.34 | Aug 29 2017

TOP STORY

Glycoprotein 2 Is a Specific Cell Surface Marker of Human Pancreatic Progenitors

Researchers report the use of a proteomics approach to phenotypically characterize human pluripotent stem cell-derived pancreatic progenitors (PPs) and distinguish these cells from non-PP populations during differentiation. Their analysis identified the pancreatic secretory granule membrane major glycoprotein 2 as a PP-specific cell surface marker. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Inhibition of 12/15-Lipoxygenase Protects against β Cell Oxidative Stress and Glycemic Deterioration in Mouse Models of Type 1 Diabetes

12/15-lipoxygenase was induced in β cells and macrophages during type 1 diabetes and produces pro-inflammatory lipids and lipid peroxides that exacerbate β-cell dysfunction and macrophage activity. [Diabetes] Abstract

Identification of Islet-Enriched Long Non-Coding RNAs Contributing to β-Cell Failure in Type 2 Diabetes

Scientists identified novel islet long non-coding RNAs differently expressed in type 2 diabetes models and investigated their role in β-cell failure and in the development of the disease. [Mol Metab] Full Article

Optogenetic Regulation of Insulin Secretion in Pancreatic β-Cells

Investigators hypothesized that a photoactivatable adenylyl cyclase (PAC) could be employed to modulate cyclic AMP (cAMP) in β-cells with light thereby enhancing insulin secretion. The PAC gene from Beggiatoa (bPAC) was delivered to β-cells. The expression and activation of bPAC increased cAMP and insulin secretion in murine islets and in β-cell pseudoislets, which displayed a more pronounced light-triggered hormone secretion compared to that of β-cell monolayers. [Sci Rep] Full Article

Small Molecule AT7867 Proliferates PDX1-Expressing Pancreatic Progenitor Cells Derived from Human Pluripotent Stem Cells

Scientists developed and performed cell-based screens to identify small molecules that induce the proliferation of human induced pluripotent stem cell-derived PDX1-expressing pancreatic progenitor cells (PPCs). The screening identified AT7867, which promoted PPC proliferation approximately five-fold within six days through the maintenance of a high Ki67⁺ cell ratio. [Stem Cell Res] Full Article

Differential Regulation of Pro-Inflammatory Cytokine Signaling by PTPs in Pancreatic β-Cells

Investigators observed expression of PTPN6 and PTPN1 in human islets and islets from non-obese diabetic mice. To clarify the role of these protein tyrosine phosphatases (PTPs) in β-cells/islets, they took advantage of CRISPR/Cas9 technology and pharmacological approaches to inactivate both proteins. [J Mol Endocrinol] Abstract

Locally Produced Xenin and the Neurotensinergic System in Pancreatic Islet Function and β-Cell Survival

Islet distribution and effects of the neurotensin (NT) receptor modulators, xenin and NT, were examined. Xenin, but not NT, significantly improved glucose disposal and insulin secretion, in mice. Xenin augmented rodent and human β-cell proliferation, whereas NT displayed proliferative actions only in human β-cells. [Biol Chem] Abstract

PANCREATIC CANCER

Inhibiting Heat Shock Protein 90 and the Ubiquitin-Proteasome Pathway Impairs Metabolic Homeostasis and Leads to Cell Death in Human Pancreatic Cancer Cells

It was hypothesized that ganetespib (Gan) plus carfilzomib (Carf) would elicit potent antitumor activity by modulating complementary homeostatic processes. In vitro and in vivo effects of this combination on mechanisms of cell growth and viability were evaluated with human pancreatic cancer cell lines. [Cancer] Abstract

Novel Histone Deacetylase Inhibitor AR-42 Exhibits Antitumor Activity in Pancreatic Cancer Cells by Affecting Multiple Biochemical Pathways

Researchers explored antitumor activity of the novel histone deacetylases inhibitor AR-42 in pancreatic cancer. AR-42 inhibited pancreatic cancer cell proliferation by causing G2/M cell cycle arrest via regulating expression levels of genes and proteins involved in cell cycle. AR-42 also induced reactive oxygen species generation and DNA damage, triggering apoptosis of pancreatic cancer cells via both caspase-3-dependent and caspase-3-independent pathways. [PLoS One] Full Article

Inhibition of ROCK1 Kinase Modulates both Tumor Cells and Stromal Fibroblasts in Pancreatic Cancer

Increased Rho-associated coiled coil-containing protein kinase (ROCK) expression has been reported in multiple pathological conditions, including cancer. Scientists report increased expression of ROCK 1 in pancreatic tumor epithelial cells as well as in cancer associated fibroblasts. [PLoS One] Full Article

Stem Cell Derived Exosomes: A Novel Vector for Tissue Repair and Diabetic Therapy

The immunomodulatory and reparative properties of stem cell-derived exosomes could protect, or even restore an early stage type-1 diabetic patient’s original islets from autoimmune destruction. Exosomes could also possibly suppress graft rejection of pancreatic islet transplants. Development of novel therapies using exosomes is slowed by a limited understanding of their mechanisms. [J Mol Endocrinol] Abstract

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McIndoe Awarded $12.8 Million Grant to Continue to Lead National Consortium on Diabetic Complications

Dr. Richard A. McIndoe, bioinformatics expert and associate director of the Center for Biotechnology and Genomic Medicine at the Medical College of Georgia at Augusta University, has received a $12.8 million grant to continue to lead a national research initiative focused on reducing the complications of diabetes. [Augusta University] Press Release

An Eye Towards Islets

The National Science Foundation has funded a multi-university study led by researchers at the University of Pittsburgh Swanson School of Engineering who are investigating the use of human pluripotent stem cells to engineer pancreatic islets in the lab. A major goal of the research is to develop a method of vascularizing islets in vitro—literally “in glass”—which studies suggest will result in higher viability and enhanced function after the transplant. [University of Pittsburg] Press Release

Firsthealth One of Two N.C. Sites for Pancreatic Cancer Clinical Trial

FirstHealth of the Carolinas is recruiting participants for the CanStem111P trial that will investigate which is more effective: the current standard chemotherapy regimen (nab-paclitaxel and gemcitabine) or the standard regimen used in combination with BB1-608. BB1-608 is a newly discovered drug that may treat cancer by targeting cancer stem cells, the highly malignant cells that are believed to be responsible for the growth, relapse and spread of many cancers. Other research studies indicate it may be a potential treatment for pancreatic cancer. [FirstHealth of the Carolinas, Inc.] Press Release

Statement from FDA Commissioner Scott Gottlieb, M.D. on the FDA’s New Policy Steps and Enforcement Efforts to Ensure Proper Oversight of Stem Cell Therapies and Regenerative Medicine

In the last few days alone, the FDA has taken steps in Florida and California to address a number of especially troubling products being marketed. But unfortunately, these are examples of a larger pool of actors who claim that their unproven and unsafe products will address a serious disease, but instead put patients at significant risk. [U.S. Food and Drug Administration] Editorial

FDA Warns US Stem Cell Clinic of Significant Deviations

The U.S. FDA posted a warning letter issued to US Stem Cell Clinic of Sunrise, Florida, and its Chief Scientific Officer Kristin Comella for marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements, including some that could impact the sterility of their products, putting patients at risk. [U.S. Food and Drug Administration] Editorial

NEW Keystone Symposia: Frontiers in Islet Biology and Diabetes
February 4-8, 2018
Keystone, Colorado, United States

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NEW Postdoctoral Training Fellow – Systems and Precision Cancer Medicine (Institute of Cancer Research)

NEW Faculty Position – Cancer Biology (The University of Texas Southwestern)

Postdoctoral Research Scientist – Tumor Environment (Cancer Research UK Beatson Institute)

Postdoctoral Position – Islet Biology (Sanofi)

Postdoctoral Scientist – hPSC Differentiation into Beta Cells (Helmholtz Zentrum München)

Postdoctoral Fellow – Pancreatic Cancer (Fred Hutchinson Cancer Research Center)

Scientist – Diabetes and Obesity (Helmholtz Zentrum München)

Assistant Investigator – Cancer Genetics, Epigenetics and Biomarkers (Baylor Research Institute)

Postdoctoral Fellow – Cancer Genetics, Epigenetics and Biomarkers (Baylor Research Institute)

Research Assistant – Cancer Genetics, Epigenetics and Biomarkers (Baylor Research Institute)

Postdoctoral Scholar – Pancreatic and Lung Cancer Research (University of California, San Francisco)

Postdoctoral Position – Immunology (Harvard Medical School)

Faculty Positions – Diabetes, Obesity, and Metabolism (University of Pittsburgh)

Postdoctoral Research Position – Pancreatic Cancer Metabolism (Eppley Institute for Research in Cancer)

Postdoctoral Research Scientist – Mechanisms of Obesity and Diabetes (NYU Langone Medical Center)

Postdoctoral Researcher – Obesity and Diabetes (University of Iowa)

Assistant Professor – Metabolic Disorders (Umeå University)

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