Pancreatic Cell News Volume 4.12 | Apr 2 2013

DIABETES

Marked Expansion of Exocrine and Endocrine Pancreas with Incretin Therapy in Humans with Increased Exocrine Pancreas Dysplasia and the Potential for Glucagon-Producing Neuroendocrine Tumors
Controversy exists regarding the potential regenerative influences of incretin therapy on pancreatic β cells versus possible adverse pancreatic proliferative effects. Examination of pancreata from age matched organ donors with type 2 diabetes (DM) treated by incretin therapy or other therapy and non diabetic controls revealed a ~40% increased pancreatic mass in DM treated with incretin therapy with both increased exocrine cell proliferation and dysplasia (increased pancreatic intraepithelia neoplasia). [Diabetes] Abstract

Predominance of β-Cell Neogenesis Rather than Replication in Humans with an Impaired Glucose Tolerance and Newly Diagnosed Diabetes
Researchers evaluated the β-cell mass and the incidence of β-cell neogenesis, replication, and apoptosis at both the prediabetic and diabetic stages. The relative β-cell area decreased and the β-cell apoptosis increased during the development of diabetes. The number of single and clustered β-cells, some of which coexpressed nestin, increased in the patients with impaired glucose tolerance and newly diagnosed diabetes. [J Clin Endocr Metab] Abstract

Effects of Surface Camouflaged Islet Transplantation on Pathophysiological Progression in a db/db Type 2 Diabetic Mouse Model
To investigate the inhibition effects of pancreatic islet transplantation on the progression of obese type 2 diabetes, scientists analyzed the effects of surface camouflaged islet transplantation on delaying the disease progression in a db/db diabetic mouse model. Surface modification using 6-arm-PEG-catechol effectively inhibited the immune cell infiltration and activation of host immune cells when immunosuppressive drug was given to the db/db type 2 diabetes mice. [Biochem Bioph Res Co] Abstract

Evaluation of Hypoglycemic and Antioxidative Effects of Synthesized Peptide MC62
Researchers investigated the hypoglycemic and antioxidative effects of peptide MC62 which was synthesized by solid phase peptide synthesis method against diabetes induced by streptozotocin. It was confirmed with the histological findings that MC62 prevented the islet from damage in diabetic mice. [Chem Biol Drug Des] Abstract

PANCREATIC CANCER

Dynamin 2 Potentiates Invasive Migration of Pancreatic Tumor Cells through Stabilization of the Rac1 GEF Vav1
The large GTPase Dynamin 2 (Dyn2) is markedly upregulated in pancreatic cancer, is a potent activator of metastatic migration, and is required for Rac1-mediated formation of lamellipodia. Investigators demonstrated an unexpected mechanism of Dyn2 action in these contexts via direct binding to the Rac1 guanine nucleotide exchange factor (GEF) Vav1. Surprisingly, disruption of the Dyn2-Vav1 interaction targets Vav1 to the lysosome for degradation via an interaction with the cytoplasmic chaperone Hsc70, resulting in a dramatic reduction of Vav1 protein stability. [Dev Cell] Abstract | Graphical Abstract | Full Article

TRPV1 and TRPA1 Antagonists Prevent the Transition of Acute to Chronic Inflammation and Pain in Chronic Pancreatitis
Using a mouse model of chronic pancreatitis produced by repeated episodes of caerulein-induced AP (AP), researchers studied the involvement of these transient receptor potential (TRP) channels in pancreatic inflammation and pain-related behaviors. Six bouts of AP increased pancreatic inflammation and pain-related behaviors, produced fibrosis and sprouting of pancreatic nerve fibers, and increased TRPV1 and TRPA1 gene transcripts and a nociceptive marker, pERK, in pancreas afferent somata. [J Neurosci] Abstract

CXCR2 Macromolecular Complex in Pancreatic Cancer: A Potential Therapeutic Target in Tumor Growth
Using a series of biochemical assays, scientists demonstrated that CXCR2 is physically coupled to its downstream effector PLC-β3 that is mediated by PDZ scaffold protein NHERF1 into a macromolecular signaling complex both in vitro and in pancreatic cancer cells. [Transl Oncol] Abstract | Full Article

Type IV Collagen Stimulates Pancreatic Cancer Cell Proliferation, Migration, and Inhibits Apoptosis through an Autocrine Loop
The cellular effects of type IV collagen were studied in pancreatic cancer cell lines by reducing type IV collagen expression through RNA interference and by functional receptor blocking of integrins and their binding-sites on the type IV collagen molecule. Scientists showed that type IV collagen is expressed close to the cancer cells in vivo, forming basement membrane like structures on the cancer cell surface that colocalize with the integrin receptors. [BMC Cancer] Abstract | Full Article

Chidamide, a Novel Histone Deacetylase Inhibitor, Synergistically Enhances Gemcitabine Cytotoxicity in Pancreatic Cancer Cells
Scientists sought to determine the antitumor effects of a novel histone deacetylase inhibitors, chidamide, in pancreatic cancer cells alone or in combination with gemcitabine. Treatments of BxPC-3 or PANC-1 pancreatic cancer cell lines with chidamide resulted in dose- and time-dependent growth arrest, accompanied by induction of p21 expression. [Biochem Bioph Res Co] Abstract

The Protective Effects of Taurine on Experimental Acute Pancreatitis in a Rat Model
Scientists investigated the protective effects of taurine (Tau) on experimental acute pancreatitis (AP) in a rat model by measuring cytokines and oxidant stress markers. The results showed that Tau reduces lipid peroxidation, amylase and myeloperoxidase activities and the concentrations of proinflammatory cytokines secondary to AP and also increased superoxide dismutase and glutathione peroxidase activities in rats with sodium taurocholate-induced AP. [Hum Exp Toxicol] Abstract

REVIEWS

Notch Signaling in Pancreatic Cancer: Oncogene or Tumor Suppressor?
The authors summarize the current literature describing Notch signaling in the development of pancreatic ductal adenocarcinoma, and discuss the potential of the Notch pathway as a therapeutic target. [Trends Mol Med] Abstract

New Insights into Pancreatic Cancer-Induced Paraneoplastic Diabetes
Emerging evidence now indicates that pancreatic cancer causes diabetes. As in type 2 diabetes, β-cell dysfunction and peripheral insulin resistance are seen in pancreatic cancer-induced diabetes. [Nat Rev Gastro Hepat] Abstract

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

Ronald DePinho, M.D., Selected for Prestigious Agilent Technologies Thought Leader Award
In recognition of his leadership of an innovative translational research program targeted at pancreatic cancer, Ronald DePinho, M.D., president of The University of Texas MD Anderson Cancer Center, was selected for the prestigious Agilent Thought Leader Award. [The University of Texas MD Anderson Cancer Center]
Press Release

U.S. FDA Approves INVOKANA™ (Canagliflozin) for the Treatment of Adults with Type 2 Diabetes
Janssen Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA) has approved INVOKANA™ (canagliflozin) for the treatment of adults with type 2 diabetes. INVOKANA™ is the first in a new class of medications called sodium glucose co-transporter 2 inhibitors to be approved in the United States. It is also the only oral, once-daily medication available in the United States offering improved glycemic control while also showing reduced body weight and systolic blood pressure in clinical trials. [Janssen Pharmaceuticals, Inc.] Press Release

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 EASD Islet Study Group Annual Meeting
September 27-29, 2013
Barcelona, Spain

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

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

Postdoctoral Fellowship – Developmental Biology/Biophysics (University of Copenhagen)

Scientist/Specialist – Mitochondrial Function (The Nestlé Institute of Health Sciences)

Research Associate (Imperial College London – Faculty of Medicine)

Postdoctoral Position – Basic Diabetes Research (Université Libre de Bruxelles)

Postdoctoral Position – Pancreatic Cancer (UT Southwestern Medical Center at Dallas)

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