Pancreatic Cell News Volume 10.27 | Jul 16 2019

TOP STORY

Loss of Setd2 Promotes Kras-Induced Acinar-to-Ductal Metaplasia and Epithelial-Mesenchymal Transition during Pancreatic Carcinogenesis

Mechanistically, Setd2 loss in acinar cells facilitated Kras-induced acinar-to-ductal reprogramming, mainly through epigenetic dysregulation of Fbxw7. Moreover, Setd2 ablation in pancreatic cancer cells enhanced epithelial-mesenchymal transition through impaired epigenetic regulation of Ctnna1. [Gut] Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Patient-Derived Pancreas-on-a-Chip to Model Cystic Fibrosis-Related Disorders

Researchers present an in vitro co-culturing system, pancreas-on-a-chip. Furthermore, they present an efficient method to micro dissect patient-derived human pancreatic ducts from pancreatic remnant cell pellets, followed by the isolation of pancreatic ductal epithelial cells. [Nat Commun] Full Article

Regulation of Glucose-Dependent Golgi-Derived Microtubules by cAMP/EPAC2 Promotes Secretory Vesicle Biogenesis in Pancreatic β-Cells

Investigators found that when glucose metabolism induced insulin secretion, it also increased formation of Golgi-derived microtubules (GDMTs), notably with the same biphasic kinetics as insulin exocytosis. Furthermore, GDMT nucleation was controlled by a glucose signal-transduction pathway through cAMP and its effector EPAC2. [Curr Biol] Full Article | Graphical Abstract

FOXA2 Is Required for Enhancer Priming during Pancreatic Differentiation

The authors mapped the dynamic chromatin landscape associated with sequential stages of pancreatic differentiation from human pluripotent stem cells. Their analysis of chromatin accessibility dynamics led them to uncover a requirement for FOXA2, known as a pioneer factor, in human pancreas specification not previously shown from mouse knockout studies. [Cell Rep] Full Article | Graphical Abstract

eIF4G1 and Carboxypeptidase E Axis Dysregulation in O-GlcNAc Transferase-Deficient Pancreatic β-Cells Contributes to Hyperproinsulinemia in Mice

Scientists showed that although carboxypeptidase E (CPE) was not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eukaryotic translation initiation factor 4 γ 1 (eIF4G1), previously shown to regulate CPE translation in β-cells, increased islet CPE levels and fully reversed OGlcNAc transferase islet-induced hyperproinsulinemia. [J Biol Chem] Abstract

A Gene Expression Network Analysis of the Pancreatic Islets from Lean and Obese Mice Identifies Complement 1q Like-3 Secreted Protein as a Regulator of β-Cell Function

Biological validation showed that complement 1q like-3 (C1ql3) was expressed in β-cells, and that it inhibited insulin secretion and key genes that are involved in β-cell function. Moreover, the increased expression of C1ql3 was correlated with the reduced insulin secretion in islets of obese mice. [Sci Rep] Full Article

Glucose, Adrenaline and Palmitate Antagonistically Regulate Insulin and Glucagon Secretion in Human Pseudoislets

Researchers present a simple method of pseudoislet formation from human islet cells and assess the transcriptome and function of isolated human islets and pseudoislets from the same organ donors. Following pseudoislet formation, insulin content/DNA and mRNA/RPS13 resembled that of islets. [Sci Rep] Full Article

The Autonomic Nervous System Regulates Pancreatic β-Cell Proliferation in Adult Male Rats

In isolated islets, muscarinic stimulation increased, whereas adrenergic stimulation decreased, glucose-induced β-cell proliferation. Blocking α-adrenergic receptors reversed the effect of epinephrine on glucose + nonesterified fatty acids-induced β-cell proliferation, whereas activation of β-adrenergic receptors was without effect. [Am J Physiol Endocrinol Metab] Full Article

DYRK1A Aggravates β Cell Dysfunction and Apoptosis by Promoting the Phosphorylation and Degradation of IRS2

Investigators observed that the overexpression of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) greatly aggravated β-cell apoptosis. Most importantly, they found that DYRK1A directly interacted with insulin receptor substrate-2 (IRS2) and promoted IRS2 phosphorylation, leading to the proteasomal degradation of IRS2 and promotion of β-cell dysfunction and apoptosis. [Exp Gerontol] Abstract

PANCREATIC CANCER

Epigenetic Reprogramming of Primary Pancreatic Cancer Cells Counteracts Their In Vivo Tumorigenicity

Scientists reprogrammed human pancreatic ductal adenocarcinoma (PDAC) cultures using three different techniques- lentivirally via induction of Yamanaka Factors, the pluripotency-associated gene OCT4 and the microRNA mir-302, or using episomal vectors as a safer alternative without genomic integration. They found that induction with episomal vectors was the most efficient method to reprogram primary human PDAC cultures as well as primary human fibroblasts that served as positive controls. [Oncogene] Abstract

Soluble UL16-Binding Protein 2 Is Associated with a Poor Prognosis in Pancreatic Cancer Patients

Soluble UL16-binding protein (ULBP)2, but neither soluble ULBP1 nor soluble ULBP3, was detected in the supernatants of pancreatic cancer cells. Soluble ULBP2 derived from pancreatic cancer cells could reduce the cytotoxicity of natural killer cells. [Biochem Biophys Res Commun] Abstract

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NF-κB/Rel Transcription Factors in Pancreatic Cancer: Focusing on RelA, C-Rel, and RelB

The authors discuss recent knowledge highlighting the role of Rel transcription factors (TFs) RelA, RelB, and c-Rel in pancreatic ductal adenocarcinoma (PDAC) development and maintenance. Next to providing rationales for therapeutically harnessing Rel TF function in PDAC, they compile strategies currently in (pre-)clinical evaluation. [Cancers] Full Article

Extracellular Matrix-Associated Factors Play Critical Roles in Regulating Pancreatic β-Cell Proliferation and Survival

The islet micro-environment greatly influences β-cell survival and proliferation. Within the islet, β-cells contact the extracellular matrix, which is deposited primarily by intra-islet endothelial cells, and this interaction has been shown to modulate proliferation and survival. [Endocrinology] Abstract

How, When, and Where Do Human β-Cells Regenerate?

In humans, β-cell mass appears to be largely defined in the postnatal period and this early replicative and generative phase is followed by a refractory state which persists throughout life. Despite this, efforts to identify physiological and pharmacological factors which might re-initiate β-cell replication are beginning to bear fruit. [Curr Diab Rep] Abstract

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

Clinical Trial for New Anti-Obesity Drug Ready to Launch at U of A

The Alberta Diabetes Institute (ADI) will be at the center of a new clinical trial for an anti-obesity drug targeting people with rare genetic conditions that contribute to their obesity. Led by Andrea Haqq, clinical scientist at the ADI and associate professor in the University of Alberta’s (U of A) Department of Pediatrics, the drug trial will also be tied to a genetic study already underway attempting to create a more comprehensive picture of the genes that are linked to obesity. [The University of Alberta] Press Release

Propanc Biopharma Provides Update on Preparation of PRP for Clinical Trial Application Submission

Propanc Biopharma, Inc. provided an update on their preparation of PRP, its anti-cancer lead product candidate, for clinical trial application submission and its recently completed reverse stock split. Propanc plans to submit its first clinical trial application in the second half of 2019, followed by commencement of a First-in-Human study in advanced cancer patients for PRP during the first half of 2020. [Propanc Biopharma, Inc.] Press Release

University of California Loses Access to New Journal Articles Published by Elsevier after Research Access Fight

Researchers in the University of California system lost subscription access to the major publisher Elsevier, the result of a closely watched fight between the two parties over how academic research should get read and paid for. [STAT News] Editorial

Sweden Passes Law for National Research Misconduct Agency

After several high-profile cases, the country’s government is creating a board to oversee and investigate all serious allegations of scientific misconduct. [The Scientist] Editorial

As Visa Difficulties Persist, Scientists Push for Change

Individual researchers and science societies are finding solutions so colleagues around the globe can attend conferences, from remote presentations to relocating conferences. [The Scientist] Editorial

NEW Pancreatic Cancer: Advances in Science and Clinical Care
September 6-9, 2019
Boston, Massachusetts, United States

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

NEW Research Associate – Pathology and Treatment of Diabetes (King’s College London)

Postdoctoral Fellowship – Jak-Stat Signaling in Prostate/Pancreatic Cancer (Medical College of Wisconsin)

PhD Studentship – Type 2 Diabetes (University of Roehampton)

Research Scientist – Endocrine Pancreas Development (Helmholtz Zentrum München)

Postdoctoral Position – Immunology (Roswell Park Cancer Institute)

Postdoctoral Researcher – Pancreas Cancer Research (Fred Hutchinson Cancer Research Center)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Postdoctoral Fellow – Cancer Drug Response Research (University of Texas at Austin)

Postdoctoral Fellowship – Regenerative Medicine and Metabolic Biology (Indiana Biosciences Research Institute)

Research Positions – Pancreatic Beta-Cells (Université de Montréal)

Postdoctoral Fellow – Neuroscience and Diabetes (The Child Health Institute of New Jersey)

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