Pancreatic Cell News Volume 4.23 | Jun 18 2013

DIABETES

MicroRNA-24/MODY Gene Regulatory Pathway Mediates Pancreatic Beta-Cell Dysfunction
MicroRNA-24 was found to be highly expressed in pancreatic beta-cells and further upregulated in islets from genetic fatty or high-fat diet fed mice, and islets subject to oxidative stress. [Diabetes] Abstract

A Novel Strategy to Increase the Proliferative Potential of Adult Human β-Cells while Maintaining Their Differentiated Phenotype
Scientists engaged canonical and non-canonical Wnt signaling at the receptor level to significantly increase human β-cell proliferation while maintaining a β-cell phenotype in intact islets. They adopted a system that utilized conditioned medium from L cells that expressed Wnt3a, R-spondin-3 and Noggin. [PLoS One]
Full Article | Press Release

Enhancing Pancreatic Beta-Cell Regeneration In Vivo with Pioglitazone and Alogliptin
Researchers tested the ability of pioglitazone and alogliptin, two drugs developed for the treatment of type 2 diabetes, to enhance beta-cell regeneration, and also defined the effect of the immunosuppression with rapamycin and tacrolimus on transplanted islet beta mass. Pioglitazone alone, or in combination with alogliptin, enhanced endogenous beta-cell regeneration in streptozotocin-treated mice, while alogliptin alone had modest effects. [PLoS One] Full Article

Deletion of Retinoic Acid Receptor β (RARβ) Impairs Pancreatic Endocrine Differentiation
Scientists followed the differentiation of cultured wild-type (WT) vs. RARβ knockout (KO) embryonic stem (ES) cells into pancreatic islet cells. They found that RARβ KO ES cells show greatly reduced expression of some important endocrine markers of differentiated islet cells, such as glucagon, islet amyloid polypeptide, and insulin 1 relative to WT. [Exp Cell Res] Abstract

Experimental Diabetes Treated with Trigonelline: Effect on Key Enzymes Related to Diabetes and Hypertension, β-Cell and Liver Function
Scientists researched the effect of trigonelline (Trig) on DPP-4, α-glucosidase and angiotensin converting enzyme (ACE) activities as well as β-cells architecture, and starch and glucose tolerance test. The pancreas islet and less β-cells damage were observed after the administration of Trig to diabetic rats. [Mol Cell Biochem] Abstract

PANCREATIC CANCER

Canonical Wnt Signaling Is Required for Pancreatic Carcinogenesis
Researchers report the results of three different approaches to inhibit the Wnt/β-catenin pathway in an established transgenic mouse model of pancreatic cancer. They found that β-catenin null cells were incapable of undergoing acinar to ductal metaplasia, a process associated with development of premalignant PanIN lesions. [Cancer Res] Abstract

Cavin-1 Is Essential for the Tumor-Promoting Effect of Caveolin-1 and Enhances Its Prognostic Potency in Pancreatic Cancer
Scientists report that cavin-1, a structural protein of caveolae, modulates the oncogenic function of caveolin-1 and cooperates with caveolin-1 to enhance pancreatic cancer aggressiveness. Cavin-1 expression is associated with caveolin-1 in pancreatic cancer tissue samples and cell lines, and predicts the metastatic potential of pancreatic cancer. [Oncogene] Abstract

Cannabinoids Inhibit Energetic Metabolism and Induce AMPK-Dependent Autophagy in Pancreatic Cancer Cells
Researchers used cannabinoids specific for CB1 and CB2 receptors and metabolomic analyses to unravel the potential pathways mediating cannabinoid-dependent inhibition of pancreatic cancer cell growth. Panc1 cells treated with cannabinoids show elevated AMP-activated protein kinase (AMPK) activation induced by a resctive oxygen species-dependent increase of AMP/ATP ratio. [Cell Death Dis] Full Article

Snail Cooperates with KrasG12D to Promote Pancreatic Fibrosis
Investigators established an in vitro model to examine the effect of Snail expression in pancreatic cancer cells on stellate cell collagen production. Snail expression in pancreatic cancer cells increased TGF-β2 levels and conditioned media from Snail-expressing pancreatic cancer cells increased collagen production by stellate cells. [Mol Cancer Res] Abstract

MUC1 Induces Drug Resistance in Pancreatic Cancer Cells via Upregulation of Multidrug Resistance Genes
Investigators report that pancreatic cancer cells that express high levels of MUC1 exhibit increased resistance to chemotherapeutic drugs (gemcitabine and etoposide) in comparison with cells that express low levels of MUC1. [Oncogenesis] Full Article

REVIEWS

The Interplay between the Gut Microbiota and the Immune System in the Mechanism of Type 1 Diabetes
This review discusses recent data linking the intestinal microbiome with mechanisms of inflammation and islet destruction. [Curr Opin Endocrinol Diabetes Obes] Abstract

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

Merck Welcomes Independent Review of the Safety Profile of JANUVIA^® (Sitagliptin) and Other Diabetes Medicines
Merck issued a statement regarding this week’s NIDDK-NCI Workshop and the American Diabetes Association’s (ADA) call for an independent review of data about the safety of incretin-based diabetes medicines, including GLP-1 analogs and DPP-4 inhibitors such as JANUVIA^® (sitagliptin). [Merck Sharp & Dohme Corp.] Press Release

MedImmune, AstraZeneca’s Biologics Arm, and NGM Biopharmaceuticals Announce Agreement to Discover and Develop Therapies for Diabetes and Obesity
AstraZeneca announced that MedImmune and NGM Biopharmaceuticals, Inc. have entered into an exclusive agreement to discover, develop and commercialize novel therapeutics from NGM’s enteroendocrine cell program for the treatment of type 2 diabetes and obesity. [AstraZeneca] Press Release

MannKind Completes Phase III Clinical Study of AFREZZA in Patients with Type 2 Diabetes
MannKind Corporation announced that all follow-up visits have been completed for the patients enrolled in Study 175, a Phase III clinical study of AFREZZA^® inhalation powder, an investigational, ultra rapid-acting mealtime insulin therapy, administered using MannKind’s next-generation inhaler. [MannKind Corporation] Press Release

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National Institutes of Health (United States)

Food and Drug Administration (United States)
 
Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW Cold Spring Harbor Laboratory: Cell Death
October 8-12, 2013
Cold Spring Harbor, United States

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

NEW Postdoctoral Research Fellow – Platelet Biology and Diabetes (Thomas Jefferson University, Cardeza Foundation for Hematologic Research)

Postdoctoral Researcher – Experimental Diabetes and Protein Research (Lund University/Experimental Medical Science)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Diabetes UK PhD Studentship (Diabetes UK)

Postdoctoral Fellow – Beta Cell Biology (Sanford Research/University of South Dakota)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

PhD Positions – Molecular Mechanisms Controlling Acinar Cell Proliferation (University Hospital Zuerich)

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


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