Pancreatic Cell News Volume 4.10 | Mar 19 2013

DIABETES

Cytoplasmic-Nuclear Trafficking of G1/S Cell Cycle Molecules and Adult Human Beta Cell Replication: A Revised Model of Human Beta Cell G1/S Control
Researchers asked whether G1/S molecules might traffic into and out of the cytoplasmic compartment in association with activation of cell cycle progression. Cdk6 and cyclin D3 were used to drive human beta cell proliferation, and promptly translocated into the nucleus in association with proliferation. [Diabetes] Abstract

X-Box Binding Protein 1 Is Essential for Insulin Regulation of Pancreatic Alpha Cell Function
To evaluate the role of X-box binding protein 1 (XBP1) in α-cells, scientists created complementary in vivo (α-cell specific XBP1 knockout mice) and in vitro (stable XBP1 knock down α-cell line, αXBPKD) models. αXBPKD cells exhibited activation of IRE1, an upstream activator of XBP1, leading to phosphorylation of JNK. [Diabetes] Abstract

Notch-Mediated Post-Translational Control of Ngn3 Protein Stability Regulates Pancreatic Patterning and Cell Fate Commitment
In addition to its ability to promote endocrine fate, scientists provided evidence of a competing ability of Ngn3 in the patterning of multipotent progenitor cells in turn controlling the formation of ducts. [Dev Biol] Abstract

Activin A, Exendin-4 and Glucose Stimulate Differentiation of Human Pancreatic Ductal Cells
Researchers investigated whether treatment of human pancreatic ductal cells with activin A and exendin-4 stimulated transdifferentiation of the cells, both in vitro and in vivo. Co-treatment of mice with activin A and exendin-4 promoted cell proliferation, induced expression of pancreatic β-cell specific markers, and caused glucose-induced insulin secretion compared with the activin A or exendin-4 mono-treatment groups, respectively. [J Endocrinol] Abstract

Effects of Lipotoxicity on Novel Insulin Secreting Human Pancreatic β-Cell Line, 1.1B4
Researchers investigated the cellular responses of 1.1B4 cells to lipotoxicity. Chronic 18 h exposure of 1.1B4 cells to 0.5 mM palmitate resulted in decreased cell viability and insulin content. [Biol Chem]
Abstract | Full Article

PACAP Inhibits β-Cell Mass Expansion in a Mouse Model of Type II Diabetes: Persistent Suppressive Effects on Islet Density
Investigators evaluated the effects of pancreatic overexpression of pituitary adenylate cyclase-activating polypeptide (PACAP) on morphometric changes of islets in a severe type II diabetes model. Histomorphometric analyses revealed significant suppression of islet mass expansion in PACAP/+:A^y/+ mice compared with A^y/+ mice at 11 months, but no significant difference between PACAP/+ and +/+ (wild-type) mice, as previously reported. [Front Endocrinol] Abstract | Full Article

PANCREATIC CANCER

Loss of the Transcription Factor GLI1 Identifies a Signaling Network in the Tumor Microenvironment Mediating KRAS-Induced Transformation
Scientists provide evidence of a novel signaling network regulated by the transcription factor GLI1 mediating KRAS-induced carcinogenesis. Using pancreatic cancer as a model, a disease with high prevalence of KRAS mutations, they showed that loss of GLI1 blocks the progression of KRAS-induced pancreatic preneoplastic lesions in mice with pancreas specific Cre-activated oncogenic mutant KRAS. [J Biol Chem]
Abstract | Full Article

Inhibiting the Growth of Pancreatic Adenocarcinoma In Vitro and In Vivo through Targeted Treatment with Designer Gold Nanotherapeutics
Researchers demonstrated in this study that the gold nanoparticle-based therapeutic containing gemcitabine inhibited tumor growth in an advanced stage of the disease in an orthotopic model of pancreatic cancer. [PLoS One] Full Article

Inhibition of Telomerase Activity by Oleanane Triterpenoid CDDO-Me in Pancreatic Cancer Cells Is ROS-Dependent
Scientists investigated the role of reactive oxygen species (ROS) in inhibition of telomerase by methyl-2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oate (CDDO-Me). Treatment of MiaPaCa-2 and Panc-1 pancreatic cancer cell lines with CDDO-Me induced the production of hydrogen peroxide and superoxide anions and inhibited the telomerase activity. [Molecules] Abstract | Full Article

Beclin1 Inhibition Promotes Autophagy and Decreases Gemcitabine-Induced Apoptosis in Miapaca2 Pancreatic Cancer Cells
Investigators observed that Beclin1 silence promoted microtubule-associated protein 1 light chain 3-II (LC3-II) protein formation and increased punctate fluorescent signals in Miapaca2 cells transfected with green fluorescent protein-tagged LC3. Beclin1 inhibition showed a greater suppressive effect on Gemcitabine-induced apoptosis of Miapaca2 cells. [Cancer Cell Int] Abstract | Full Article

REVIEWS

Role of Insulin and Igf Signaling in Pancreatic Cancer
The authors focus on the contribution of insulin and insulin-like growth factors (IGFs) to carcinogenesis in the insulin-producing organ, the pancreas. [J Mol Endocrinol] Abstract | Full Article

Diabetes Mellitus and Inflammation
Type 2 diabetes mellitus is increasingly common worldwide. Related complications account for increased morbidity and mortality, and enormous healthcare spending. Knowledge of the pathophysiological derangements involved in the occurrence of diabetes and related complications is critical for successful prevention and control solutions. [Curr Diabetes Rep] Abstract

Queen Mary Scientists Receive over £500,000 for Pancreatic Cancer Research
Three scientists from Queen Mary, University of London, have received grants totalling £540,000 from the Pancreatic Cancer Research Fund to carry out ground-breaking research to improve the prognosis of the disease. [Queen Mary University of London] Press Release

Indiana University Researchers Earn $3.2 Million Grant to Develop, Improve Therapies for Pancreatic Cancer
Two Indiana University researchers have been awarded a multi-year, $3.2 million grant to develop and improve therapies for pancreatic cancer, the fourth leading cause of cancer death in the United States. [Indiana University] Press Release

Boehringer Ingelheim and Lilly Initiate MARLINA™ Clinical Trial to Evaluate Use of Trajenta® (Linagliptin) in Patients with Type 2 Diabetes and Albuminuria
Boehringer Ingelheim and Eli Lilly and Company announced the initiation of a Phase IIIb trial to evaluate the glycemic efficacy and safety of linagliptin in type 2 diabetes patients with prevalent albuminuria in addition to current standard therapy for diabetic nephropathy. [Boehringer Ingelheim GmbH] Press Release

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NEW The 2013 Digestive Disease Week
May 18-21, 2013
Orlando, United States

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

Postdoctoral Position – Pancreatic Beta-Cell Dysfunction (Weill Cornell Medical College)

Postdoctoral Position – Pancreas Development (INSERM)

PhD Studentship – Developmental Genes in Adult Pancreas Homeostasis & Energy Metabolism (Helmholtz Zentrum München)

Postdoctoral Position – Mechano-Signaling in the Regulation of Pancreatic Cancer Progression (Fox Chase Cancer Center)

Postdoctoral Position (New York University)

PhD position (University Hospital Wuerzburg)

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