Pancreatic Cell News Volume 4.14 | Apr 16 2013

DIABETES

Pancreatic Beta-Cell Response to Increased Metabolic Demand and to Pharmacologic Secretagogues Requires EPAC2A
Scientists conducted in vitro studies of glucose-stimulated insulin secretion and calcium dynamics in isolated EPAC2A-deficient islets. They report that EPAC2A deficiency does not impact glucose-stimulated insulin secretion in mice under basal conditions. [Diabetes] Abstract | Press Release

Conversion of Mature Human β-Cells into Glucagon-Producing α-Cells
Researchers examined the plasticity of human insulin-producing β-cells in a model of islet cell aggregate formation. They showed that primary human β-cells can undergo a conversion into glucagon-producing α-cells without introduction of any genetic modification. [Diabetes] Abstract

Inhibition of Instant Blood-Mediated Inflammatory Responses by Co-Immobilization of sCR1 and Heparin on Islets
Researchers previously developed a method of co-immobilizing sCR1 and heparin on islets. They examined whether this process could reduce islet loss following intraportal islet transplantation in a syngeneic mouse model. Fibrin staining and plasma insulin measurements indicated that, compared to non-treated islets, sCR1-heparin islet transplantation was associated with fewer blood clots around islets, and significantly less insulin leakage from damaged islets at 1 h post-transplantation. [Biomaterials] Abstract

miR-135a Targets IRS2 and Regulates Insulin Signaling and Glucose Uptake in the Diabetic Gastrocnemius Skeletal Muscle
Scientists report that 41 miRNAs are altered in the diabetic gastrocnemius skeletal muscle and of these, miR-135a that is identified as a critical regulator of myogenesis, is significantly up-regulated. IRS2 is predicted as its potential putative target and its levels are down-regulated in the diabetic gastrocnemius skeletal muscle. In C2C12 cells, while miR-135a levels decreased during differentiation, IRS2 levels were up-regulated. [BBA-Mol Basis Dis] Abstract

Pancreatic Stellate Cells Reduce Insulin Expression and Induce Apoptosis in Pancreatic β-Cells
Investigators hypothesized that pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, might affect the phenotype of pancreatic β-cells. α-Smooth muscle actin (a marker of activated PSC)-positive cells were found within and around the fibrotic islets. Indirect co-culture with PSCs reduced insulin expression and induced apoptosis in RIN-5F pancreatic β-cells. [Biochem Bioph Res Co] Abstract

Basement Membrane Extract Preserves Islet Viability and Activity In Vitro by Up-Regulating α3 Integrin and Its Signal
A special reconstituted basement membrane extract (BME) that solidifies into a gel at 37^oC was used to embed isolated islets in this study. The strategy was used to re-establish the interaction between the islets and peri-islet basement membrane. Investigators report that islets embedded in BME showed lower caspase-3 levels and higher Akt activity than those in suspension. [Pancreas] Abstract

PANCREATIC CANCER

Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome
Researchers showed that menin ablation enhances Hedgehog signaling, a proproliferative and oncogenic pathway, in murine pancreatic islets. Menin directly interacts with protein arginine methyltransferase 5, a negative regulator of gene transcription. [Cancer Research] Abstract

Oxidative Stress Induced by Inactivation of TP53INP1 Cooperates with KrasG12D to Initiate and Promote Pancreatic Carcinogenesis in the Murine Pancreas
Researchers aimed  to determine whether tumor protein p53-induced nuclear protein 1 (TP53INP1) loss of expression contributes to pancreatic cancer formation in a conditional KrasG12D mouse model. They generated Kras-INP1KO mice using LSL-Kras^G12D/+;Pdx1-Cre^+/− mice (Kras mice) and TP53INP1^−/− mice. Analysis of pancreases during ageing showed that in the presence of activated Kras, TP53INP1 loss of expression accelerated pancreatic intraepithelial neoplasia 1b formation and increased pancreatic injury and the number of high-grade lesions as compared with what occurs in Kras mice. [Am J Pathol] Abstract

Evaluation of ⁸⁹Zr-Labeled Human Anti-CD147 Monoclonal Antibody as a Positron Emission Tomography Probe in a Mouse Model of Pancreatic Cancer
CD147 expression was evaluated in four pancreatic cancer cell lines (MIA Paca-2, PANC-1, BxPC-3, and AsPC-1) and a mouse cell line A4 as a negative control. Scientists report that among these, MIA Paca-2 cells showed the highest expression of CD147, while A4 cells had no expression. [PLoS One] Full Article

Notch1 Contributes to Chemoresistance to Gemcitabine and Serves as an Unfavorable Prognostic Indicator in Pancreatic Cancer
Investigators report the role of Notch1 in gemcitabine resistance and its prognostic significance in pancreatic cancer (PC). A small interfering RNA (siRNA) specifically targeting Notch1 was transiently transfected into three PC cell lines, followed by examination of chemosensitivity to gemcitabine. Successful knockdown of Notch1 by specific siRNA induced increased chemosensitivity to gemcitabine in all three cell lines. [World J Surg] Abstract

REVIEWS

More than $5 Million in Research Grants Awarded by the Pancreatic Cancer Action Network and AACR
The Pancreatic Cancer Action Network and the American Association for Cancer Research (AACR) awarded 14 grants totaling more than $5 million to outstanding scientists throughout the country, supporting their innovative research in the field of pancreatic cancer. [American Association for Cancer Research]
Press Release

The Lustgarten Foundation and Pancreatic Cancer Action Network Join Forces for ‘Unite To Fight Pancreatic Cancer’, A First of Its Kind Walk Event in Boston
The Lustgarten Foundation and the Pancreatic Cancer Action Network are proud to announce that they will join forces and efforts for Unite to Fight Pancreatic Cancer, a special walk event scheduled to take place in Boston at DCR’s Mother’s Rest Park on Saturday, September 28, 2013. [PR Newswire Association LLC] Press Release

JDRF Announces New Outreach Kit to Support Adults Newly Diagnosed with Type 1 Diabetes
JDRF announced that it has created a new resource for adults newly diagnosed with type 1 diabetes (T1D). The Adult Type 1 Pak is a sling-style bag that will include important resources and information to educate, support, and inspire adults newly diagnosed with T1D, age 16 and above. [JDRF] Press Release

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NEW ESMO 15th World Congress on Gastrointestinal Cancer
July 3-6, 2013
Barcelona, Spain

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

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

Postdoctoral Fellowship – Developmental Biology/Biophysics (University of Copenhagen)

Scientist/Specialist – Mitochondrial Function (The Nestlé Institute of Health Sciences)

Postdoctoral Position – Basic Diabetes Research (Université Libre de Bruxelles)

Postdoctoral Position – Pancreatic Cancer (UT Southwestern Medical Center at Dallas)

Postdoctoral Fellow – Pancreatic Beta Cell Regeneration and Survival (Oklahoma Medical Research Foundation)

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