Pancreatic Cell News Volume 7.16 | Apr 26 2016

KAT2B Is Required for Pancreatic Beta Cell Adaptation to Metabolic Stress by Controlling the Unfolded Protein Response
Researchers showed that germline and β cell-specific disruption of the lysine acetyltransferase 2B (Kat2b) gene in mice leads to impaired insulin secretion and glucose intolerance. [Cell Rep] Full Article | Graphical Abstract

PYY-Dependent Restoration of Impaired Insulin and Glucagon Secretion in Type 2 Diabetes following Roux-En-Y Gastric Bypass Surgery
Using the diabetic Goto-Kakizaki rat model, researchers demonstrated that Roux-en-Y gastric bypass restores normal glucose regulation of glucagon and insulin secretion and normalizes islet morphology. [Cell Rep] Full Article | Graphical Abstract

sept7b Is Required for the Differentiation of Pancreatic Endocrine Progenitors
Investigators showed, by functional manipulation techniques in transgenic zebrafish lines that suppression of sept7b, the zebrafish ortholog of human SEPT7, profoundly increased the number of endocrine progenitors but limited their differentiation, leading to reduction in β- and α-cell mass. [Sci Rep] Full Article

TCF7L2 Involvement in Estradiol- and Progesterone-Modulated Islet and Hepatic Glucose Homeostasis
To evaluate the role of transcription factor 7-like 2 (TCF7L2), a key regulator of glucose homeostasis, in estradiol (E2) and progesterone (P4)-modulated glucose metabolism, mouse insulinoma cells and human liver cancer cells were treated with physiological concentrations of E2 or P4 in the up- and down-regulation of TCF7L2. [Sci Rep] Full Article

Circulating Differentially Methylated Amylin DNA as a Biomarker of β-Cell Loss in Type 1 Diabetes
Researchers examined whether demethylated circulating free amylin DNA may serve as a biomarker of β-cell death in type 1 diabetes. β cells showed unique methylation patterns within the amylin coding region that were not observed with other tissues. [PLoS One] Full Article

Proteasome Inhibitors, Including Curcumin, Improve Pancreatic β-cell Function and Insulin Sensitivity in Diabetic Mice
Investigators showed that curcumin prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance. [Nutr Diabetes] Full Article

PANCREATIC CANCER

Identification of Pyrazolopyridazinones as PDEδ Inhibitors
The authors reported that the small-molecule Deltarasin binds to the prenyl-binding pocket of PDEδ, and impairs Ras enrichment at the plasma membrane, thereby affecting the proliferation of KRas-dependent human pancreatic ductal adenocarcinoma cell lines. Here, using structure-based compound design, they have identified pyrazolopyridazinones as a novel, unrelated chemotype that binds to the prenyl-binding pocket of PDEδ with high affinity, thereby displacing prenylated Ras proteins in cells. [Nat Commun] Full Article

Hypoxia-Induced Oxidative Stress Promotes MUC4 Degradation via Autophagy to Enhance Pancreatic Cancer Cells Survival
Scientists report that MUC4 protein stability is drastically affected in pancreatic cancer, under hypoxic condition in a hypoxia inducible factor 1α-independent manner. Mechanistically, they demonstrated that hypoxia-mediated induction of reactive oxygen species promotes autophagy by inhibiting pAkt/mTORC1 pathway, one of the central regulators of autophagy. [Oncogene] Abstract

Calcium Sensing Receptor Suppresses Human Pancreatic Tumorigenesis through a Novel NCX1/Ca²⁺/β-Catenin Signaling Pathway
The authors revealed that the expression of calcium sensing receptor was consistently downregulated in the primary cancer tissues from pancreatic cancer patients, which was correlated with tumor size, differentiation and poor survival of the patients. [Cancer Lett] Abstract

TMEM45B Promotes Proliferation, Invasion and Migration and Inhibits Apoptosis in Pancreatic Cancer Cells
Scientists showed that TMEM45B exhibited high expression in pancreatic cancer tissues and cell lines compared with the normal pancreatic tissues and cells. [Mol Biosyst] Abstract

Pancreatic Cancer
The authors summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of pancreatic cancer. In addition, they present an outline of potential future directions for research and patient management. [Nat Rev Dis Primers] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.

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ProtoKinetix Outlines Steps to Clinical Trial Application for AAGP™
ProtoKinetix, Incorporated outlined the steps to be completed for the application to conduct a clinical trial in Canada. The clinical trial application, for a Phase I/II study in patients, will involve the addition of AAGP™ to the well-established Edmonton Protocol for islet cell transplants for the treatment of type 1 diabetes. [ProtoKinetix, Incorporated (Business Wire)] Press Release

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

NEW Postdoctoral Fellow – Pancreas Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Diabetic Peripheral Neuropathy (University of North Dakota)

Postdoctoral Fellow – Abnormal Growth, Childhood Obesity and Diabetes (University of Bergen)

Lecturer – Tumor Microenvironment and Pancreatic Cancer (Queen Mary, University of London)

Group Leader – Stem Cell Biology, Pancreatic Cancer and Bioengineering (University of Copenhagen)

PhD Studentship – Regulation of Metabolism (University of Wuerzburg)

Postdoctoral Fellow – Diabetes Induced Neural Tube Defects (UMB School of Medicine)

Postdoctoral Fellow – Pancrease Preconditioning (Centre Européen d’Etude du Diabète)

Postdoctoral Fellow – Pancreatic Zinc Transporter as Therapeutic Target (Johns Hopkins School of Medicine)

Research Scientist – Various Fields (King Abdullah International Medical Research Center)

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

Master Studentship – Exercise and Diabetes (Swansea University)

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