Pancreatic Cell News Volume 6.12 | Mar 31 2015

Islet Amyloid Polypeptide Exerts a Novel Autocrine Action in β-Cell Signaling and Proliferation
Investigators explored the signaling pathways and mitogenic actions of islet amyloid polypeptide (IAPP) on β cells. They showed that IAPP activated Erk1/2 and v-akt murine thymoma viral oncogene homolog 1 at the picomolar range in mouse pancreatic islets and MIN6 β cells cultured at low glucose concentrations. [FASEB J] Abstract

Loss of Fibroblast Growth Factor 21 Action Induces Insulin Resistance, Pancreatic Islet Hyperplasia and Dysfunction in Mice
Scientists investigated the physiological role of fibroblast growth factor (FGF) 21 in pancreatic islets using FGF21-knockout mice. Glucose and insulin tolerance were assessed. Expression of genes and proteins related to islet function and underlying mechanisms were also examined. [Cell Death Dis] Full Article

Inducible VEGF Expression by Human Embryonic Stem Cell-Derived Mesenchymal Stromal Cells Reduces the Minimal Islet Mass Required to Reverse Diabetes
Scientists hypothesized that co-transplantation of islets with human embryonic stem cell-derived mesenchymal stromal cells that conditionally overexpress VEGF may augment islet revascularization and reduce the minimal islet mass required to reverse diabetes in mice. [Sci Rep] Full Article

Insulin Resistance Induces Posttranslational Hepatic Sortilin 1 Degradation in Mice
Researchers investigated the effect and molecular mechanism of insulin regulation of Sort1. Results showed that insulin induced Sort1 protein, but not mRNA, in AML12 cells. Hepatic Sort1 was down-regulated in diabetic mice, which was partially restored after the administration of the insulin sensitizer metformin. [J Biol Chem]
Abstract | Full Article

Optogenetic Control of Insulin Secretion by Pancreatic β-Cells In Vitro and In Vivo
Researchers used optogenetics to investigate whether insulin secretion and blood glucose homeostasis could be controlled by regulating intracellular calcium ion concentrations in a mouse pancreatic β-cell line transfected with the optogenetic protein channelrhodopsin-2. [Gene Ther] Abstract

PANCREATIC CANCER

Targeting of Metastasis-Promoting Tumor-Associated Fibroblasts and Modulation of Pancreatic Tumor-Associated Stroma with a Carboxymethylcellulose-Docetaxel Nanoparticle
Scientists investigated targeted depletion of stroma for pancreatic cancer therapy via taxane nanoparticles. They examined Cellax-docetaxel treatment effects in highly stromal primary patient-derived pancreatic cancer xenografts and in a metastatic PAN02 mouse model of pancreatic cancer, focusing on specific cellular interactions in the stroma, pancreatic tumor growth and metastasis. [J Control Release] Abstract

GLI2-Dependent C-MYC Upregulation Mediates Resistance of Pancreatic Cancer Cells to the BET Bromodomain Inhibitor JQ1
Researchers showed that pancreatic cancer cells developing resistance to JQ1 demonstrate cross-resistance to I-BET151 and insensitivity to BRD4 downregulation. The resistant cells maintained expression of c-MYC, increased expression of JQ1-target genes FOSL1 and HMGA2, and demonstrated evidence of epithelial-mesenchymal transition. [Sci Rep] Full Article

Hepatocyte Nuclear Factor 1A (HNF1A) as a Possible Tumor Suppressor in Pancreatic Cancer
Investigators knocked down the HNF1A gene expression in two cancer cell lines using three siRNA sequences. The impacts on cell proliferation, apoptosis, and cell cycle as well as the phosphorylation of Akt signaling transduction proteins were examined using ATP assay, flow cytometry and Western blot. [PLoS One] Full Article

A Decrease in miR-150 Regulates the Malignancy of Pancreatic Cancer by Targeting C-Myb and MUC4
Researchers set out to determine the tumorigenesis of miR-150 in pancreatic cancer. The in vitro and in vivo assays of pancreatic cancer cells showed that miR-150 overexpression leads to reduced cell growth, clonogenicity, migration, invasion, modular cell cycles, and induced apoptosis. [Pancreas] Abstract

Suppressed Expression of LDHB Promotes Pancreatic Cancer Progression via Inducing Glycolytic Phenotype
Scientists determined the roles of lactate dehydrogenase B (LDHB) in pancreatic cancer development and progression. Functional analysis revealed that suppressed expression of LDHB promoted pancreatic cancer cells proliferation, invasion, and migration in hypoxia. [Med Oncol] Abstract

12-Lipoxygenase and Islet β cell Dysfunction in Diabetes
The authors focus on the evidence supporting the proinflammatory role of 12-lipoxygenase as it relates to islet β cells, and the potential for 12-lipoxygenase inhibition as a future avenue for the prevention and treatment of metabolic disease. [Mol Endocrinol] Abstract | Full Article

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New Drug Application Approval of Zafatek^® Tablets for the Treatment of Type 2 Diabetes in Japan
Takeda Pharmaceutical Company Limited announced that the Japanese Ministry of Health, Labor and Welfare has approved the New Drug Application of Zafatek^®, a drug for treating type 2 diabetes. [Takeda Pharmaceutical Company Limited] Press Release

Type 2 Diabetes: CHMP Recommends Empagliflozin/Metformin Hydrochloride for Approval in the European Union
Boehringer Ingelheim and Eli Lilly and Company announced they have received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency, recommending approval of a single-pill combination therapy with empagliflozin/metformin hydrochloride for the treatment of adults with type 2 diabetes. [Boehringer Ingelheim GmbH] Press Release

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NEW Postdoctoral Position – Type 2 Diabetes, Obesity, and Metabolism (Boston Children’s Hospital)

NEW Postdoctoral Position – Obesity & Diabetes (INSERM U892)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

PhD Position – Lineage Reprogramming (Max Delbrück Center for Molecular Medicine)

Postdoctoral Positions – Developmental Biology (Joslin Diabetes Center)

Postdoctoral Fellow – Type 2 Diabetes (Harvard Medical School)

Tenure-Track Immunology Faculty Position – Diabetes (University of Connecticut Health Center)

Postdoctoral Position – Endothelial Dysfunction and Diabetes (Weill Cornell Medical College in Qatar)

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