Pancreatic Cell News Volume 7.09 | Mar 8 2016

A Branched-Chain Amino Acid Metabolite Drives Vascular Fatty Acid Transport and Causes Insulin Resistance
Investigators found that 3-hydroxyisobutyrate is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. [Nat Med] Abstract

Ablation of Huntingtin in Adult Neurons Is Nondeleterious but Its Depletion in Young Mice Causes Acute Pancreatitis
Using inducible Htt knockout mice, researchers found that Htt depletion does not lead to adult neurodegeneration or animal death at >4 mo of age, which was also verified by selectively depleting Htt in neurons. On the other hand, young Htt KO mice die at 2 mo of age of acute pancreatitis due to the degeneration of pancreatic acinar cells. [Proc Natl Acad Sci USA] Abstract

Use of the Fluidigm C1 Platform for RNA Sequencing of Single Mouse Pancreatic Islet Cells
The authors provided an assessment of the Fluidigm C1 platform for RNA sequencing of single mouse pancreatic islet cells. The system combined microfluidic technology and nanoliter-scale reactions. [Proc Natl Acad Sci USA] Abstract

The P72R Polymorphism of p53 Predisposes to Obesity and Metabolic Dysfunction
Investigators utilized a humanized mouse model of the p53 codon 72 variants and monitored these mice following challenge with a high-fat diet (HFD). Mice with the arginine 72 (R72) variant of p53 developed more-severe obesity and glucose intolerance on a HFD, compared to mice with the proline 72 variant (P72). R72 mice developed insulin resistance, islet hypertrophy, increased infiltration of immune cells, and fatty liver disease. [Cell Rep] Full Article | Graphical Abstract

Insulin Resistance in Human iPS Cells Reduces Mitochondrial Size and Function
To define the cause-effect relationship between insulin resistance and mitochondrial dysfunction, researchers compared mitochondrial metabolism in induced pluripotent stem cells (iPSC) from five healthy individuals and four patients with genetic insulin resistance due to insulin receptor mutations. [Sci Rep] Full Article

Genetic and Pharmacological Inhibition of Vanin-1 Activity in Animal Models of Type 2 Diabetes
The authors investigated the role of vanin-1 in the development of hepatic steatosis and insulin resistance in animal models of obesity and diabetes. [Sci Rep] Full Article

PANCREATIC CANCER

Radiation Therapy Induces Macrophages to Suppress Immune Responses against Pancreatic Tumors in Mice
Scientists investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive pancreatic ductal adenocarcinoma and accelerates progression of pre-invasive foci. [Gastroenterology] Abstract

Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions
Scientists showed that mutant KRas alters mitochondrial metabolism in pancreatic acinar cells, resulting in increased generation of mitochondrial reactive oxygen species (mROS). Mitochondrial ROS then drives the dedifferentiation of acinar cells to a duct-like progenitor phenotype and progression to PanIN. [Cell Rep] Full Article | Graphical Abstract

TAp73 Loss Favors Smad-Independent TGF-β Signaling that Drives EMT in Pancreatic Ductal Adenocarcinoma
Investigators found that loss of transcriptionally active p73 (TAp73), a p53 family member, impacted pancreatic ductal adenocarcinoma development. In two relevant and specific engineered pancreatic cancer mouse models, they observed that TAp73 deficiency reduced survival and enhanced epithelial-to-mesenchymal transition (EMT). [Cell Death Differ] Abstract

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Roche Submits Filing to FDA for HbA1c Testing Solution to Help Meet Increasing Demand for HbA1c Testing of People with Diabetes
Roche announced that it has submitted the cobas c 513 analyzer as a 510(k) to the U.S. Food and Drug Administration (FDA) as a dedicated, high-throughput HbA1c testing solution for people with diabetes. [Roche (PR Newswire Association LLC)] Press Release

Bio-Path Holdings Announces Pancreatic Cancer Research Collaboration with Leading Oncology Institution
Bio-Path Holdings, Inc., announced that it has entered a sponsored research agreement with The University of Texas MD Anderson Cancer Center to evaluate Bio-Path’s clinical pipeline for its ability to modulate pancreatic cancer. Included in the evaluation will be BP1001 (Liposomal Grb2 antisense),which is currently in a Phase II study for blood cancers. [Bio-Path Holdings] Press Release

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NEW Postdoctoral Research Fellowship – Surgical Oncology in Pancreatic Cancer (University of Nebraska Medical Center)

NEW Postdoctoral Research Fellowship – Pancreatic Progenitors in Development (Johns Hopkins University Institute of Genetic Medicine)

Postdoctoral Fellowship – Metabolism and Cancer (Monash University)

Associate Professor – Pancreatic Cancer, Stem Cell Biology and Bioengineering (University of Copenhagen)

Postdoctoral Fellowship – Mechanisms of Atherosclerosis, Diabetes and Obesity (Washington University School of Medicine)

Assistant Professor of Surgery – Molecular Biology and Pancreatic Development (University of Pittsburgh)

Postdoctoral Fellowship – Neural Mechanisms of Diabetes (Albert Einstein College of Medicine)

Faculty Position – Metabolic Disease Research (Lewis Katz School of Medicine)

Postdoctoral Fellowship – Diabetes (Danish Diabetes Academy)

Post-Doc Fellowship – Glucose Metabolism (Joslin Diabetes Center)

Post-Doc Researcher – Type 1 Diabetes (University of Turku)

MD/PhD Researcher – Biomedical Sciences (Hannover Medical School)

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