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Zai Wang, Liang Peng, Yu-Li Song, Shiqing Xu, Zhan Hua, Ni Fang, Min Zhai, Honglin Liu, Qing Fang, Tingting Deng, Wenjian Zhang, Yuan-Jia Chen, Jinning Lou
Aberrant blood vessel formation and hemorrhage may contribute to tumor progression and are potential targets in the treatment of several types of cancer. Pancreatic neuroendocrine tumors (PNETs) are highly vascularized, particularly when they are well-differentiated. However, the process of vascularization and endothelial cell detachment in PNETs is poorly understood. In the present study, 132 PNET clinical samples were examined and a special type of hemorrhagic region was observed in ~30% of the samples regardless of tumor subtype...
April 2018: Oncology Letters
Rita Sofia Garcia Ribeiro, Ashwini Ketkar-Atre, Ting Yin, Karim Louchami, Tom Struys, Ivo Lambrichts, Abdullah Sener, Willy Jean Malaisse, Marcel De Cuyper, Uwe Himmelreich
Pancreatic islets (PIs) transplantation is an alternative approach for the treatment of severe forms of type 1 diabetes (T1D). To monitor the success of transplantation, it is desirable to follow the location of engrafted PIs non-invasively. In vivo magnetic resonance imaging (MRI) of transplanted PIs is a feasible cell tracking method; however, this requires labeling with a suitable contrast agent prior to transplantation. We have tested the feasibility of cationic magnetoliposomes (MLs), compared to commercial contrast agents (Endorem and Resovist), by labeling insulinoma cells and freshly isolated rat PIs...
March 12, 2018: Journal of Personalized Medicine
Yasushi Shibasaki, Takanori Sakaguchi, Ryo Kitajima, Satoru Furuhashi, Ryota Kiuchi, Makoto Takeda, Takanori Hiraide, Yoshifumi Morita, Naoki Unno, Hiroya Takeuchi
Pancreaticoduodenal artery (PDA) aneurysm associated with celiac axis compression by the median arcuate ligament (MAL) is a rare disorder, but may be lethal if ruptured. Therefore, prophylactic surgical treatments need to be considered when MAL compresses the celiac axis. We herein report the usefulness of an arterial flow analysis for objectively evaluating this pathophysiology under four-dimensional flow-sensitive magnetic resonance imaging (4D-flow MRI). Celiac artery stenosis was incidentally found under contrast-enhanced CT in a 50-year-old woman with symptomatic solitary pancreatic insulinoma...
March 5, 2018: Clinical Journal of Gastroenterology
Yuichi Tsuchiya, Michiko Saito, Hiroshi Kadokura, Jun-Ichi Miyazaki, Fumi Tashiro, Yusuke Imagawa, Takao Iwawaki, Kenji Kohno
In mammalian pancreatic β cells, the IRE1α-XBP1 pathway is constitutively and highly activated under physiological conditions. To elucidate the precise role of this pathway, we constructed β cell-specific Ire1α conditional knockout (CKO) mice and established insulinoma cell lines in which Ire1α was deleted using the Cre-loxP system. Ire1α CKO mice showed the typical diabetic phenotype including impaired glycemic control and defects in insulin biosynthesis postnatally at 4-20 weeks. Ire1α deletion in pancreatic β cells in mice and insulinoma cells resulted in decreased insulin secretion, decreased insulin and proinsulin contents in cells, and decreased oxidative folding of proinsulin along with decreased expression of five protein disulfide isomerases (PDIs): PDI, PDIR, P5, ERp44, and ERp46...
March 5, 2018: Journal of Cell Biology
Lukas O Dialer, Andreas Jodal, Roger Schibli, Simon M Ametamey, Martin Béhé
Background: Analogues of exendin-4 have been radiolabeled for imaging the glucagon-like peptide type 1 receptors (GLP-1R) which are overexpressed in insulinoma. The aim of this research was to synthesize an18 F-labeled silicon containing exendin-4 peptide (18 F- 2 ) and to evaluate its in vitro and in vivo behavior in CHL-GLP-1 receptor positive tumor-bearing mice.18 F-labeled silicon containing exendin-4 peptide (18 F- 2 ) was prepared via one-step nucleophilic substitution of a silane precursor with18 F-fluoride in the presence of acetic acid and K222...
2018: EJNMMI Radiopharm Chem
Gong Deuk Bae, Eun-Young Park, Dong Jae Baek, Hee-Sook Jun, Oh Yoon Sin
Liquiritigenin (LQ) is a major active component of licorice root, which is a flavone used for treating many diseases, including diabetes. LQ has been shown to exhibit a glucose-lowering effect in diabetic mice. Therefore, we investigated the potential of LQ to protect against lipotoxicity-induced beta-cell apoptosis and the underlying molecular mechanisms. Exposure of INS-1 rat insulinoma cells to LQ significantly increased cell viability and blocked palmitate (PA)-induced apoptosis, as evidenced by the reduction of Annexin-V-stained cells, cleaved caspase-3 levels, and poly (ADP-ribose) polymerase (PARP) activity, as well as upregulation of Bcl-2 expression...
February 27, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hui Yi Ng, Alexia Pape
No abstract text is available yet for this article.
March 5, 2018: Medical Journal of Australia
Heather M Ames, Lisa M Rooper, John J Laterra, Charles G Eberhart, Fausto J Rodriguez
Tumors with a neuronal component comprise a small percentage of central nervous system (CNS) neoplasms overall, but the presence of neuronal differentiation has important diagnostic, prognostic, and therapeutic implications. Insulinoma-associated protein 1 (INSM1) is a transcription factor with strong nuclear immunostaining in neuroendocrine cells and neoplasms of neuroendocrine origin; however, its expression in the CNS in normal brain and in neoplastic cells has not been fully explored. Here, we present immunostaining results from a large number of archival CNS tissue specimens, including 416 tumors...
February 27, 2018: Journal of Neuropathology and Experimental Neurology
Yeong-Min Yoo, Yung Chul Park
Streptozotocin (STZ), a glucose analog, induces diabetes in experimental animals by inducing preferential cytotoxicity in pancreatic beta cells. We investigated whether STZ reduced the production of intracellular insulin through autophagy in insulinoma INS-1E cells. Typically, 2 mM STZ treatment for 24 h significantly decreased cell survival. STZ treatment led to significant decrease in phospho-AMP-activated protein kinase (p-AMPK) level; reduction in levels of phospho-protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α); significant reduction in levels of p85α, p110, phospho-serine and threonine kinase/protein kinase B (p-Akt/PKB) (Ser473), phospho-extracellular-regulated kinase (p-ERK), and phospho-mammalian target of rapamycin (p-mTOR); increase in levels of Cu/Zn-superoxide dismutase (SOD), Mn-SOD, and catalase; decrease in B-cell lymphoma 2 (Bcl-2) expression; increase in Bcl-2-associated X protein (Bax) expression; increase in levels of microtubule-associated protein 1 light chain 3 (LC3) and Beclin 1; and reduction in production of intracellular insulin...
February 27, 2018: DNA and Cell Biology
A Karatug Kacar, S Gezginci-Oktayoglu, S Bolkent
Insulinoma INS-1 cell line is a pancreatic beta cell tumor which is characterized with high insulin content and secretion in response to increasing glucose levels. 4-Methylcatechol (4-MC) is a metabolite of quercetin, which is known as a potential drug for inhibition of tumorigenesis. The aim of this study was to determine the applying doses of 4-methylcatechol (4-MC) for triggening cell death and decreasing the cell function of rat insulinoma INS-1 beta cells. The rate of apoptosis and the amount of insulin in the cell and the secretions were determined by the ELISA method...
January 1, 2018: Human & Experimental Toxicology
Vaishali I Parekh, Sita D Modali, James Welch, William Simonds, Lee Scott Weinstein, Electron Kebebew, Sunita K Agarwal
Extract: Pancreatic neuroendocrine tumors (PNETs/pNETs/p-NETs/PanNETs) are rare endocrine neoplasms that can be either functioning tumors that secrete hormones characteristic of their endocrine cell of origin, or nonfunctioning tumors. The most common functioning PNETs are the insulin-secreting b-cell tumors (insulinomas) that are mainly sporadic, but may also occur in 10% of patients with the hereditary tumor syndrome multiple endocrine neoplasia type 1 (MEN1) (OMIM ID: 131100). Patients with the MEN1 syndrome carry a heterozygous germline inactivating mutation in the MEN1 tumor suppressor gene and specific somatic loss of the normal MEN1 allele, leading to endocrine tumors mainly of the parathyroids, pituitary and pancreas (PNETs)...
February 21, 2018: Endocrine-related Cancer
A B Câmara-de-Souza, M T K Toyoshima, M L Giannella, D S Freire, C P Camacho, D M Lorenço, M S Rocha, T Bacchella, R Jureidini, M C C Machado, M Q Almeida, M A A Pereira
BACKGROUND/OBJECTIVES: Insulinoma is a rare pancreatic tumor and, usually, a benign disease but can be a malignant one and, sometimes, a highly aggressive disease. The aim of this study was to determine differences between benign and malignant tumors. METHODS: Retrospective study of 103 patients with insulinoma treated in a tertiary center. It was analyzed demographic, clinical, laboratory, localization and histologic analysis of tumor and follow up data of subjects in order to identify differences between individuals benign and malignant disease...
February 1, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Monika Hospodiuk, Madhuri Dey, Bugra Ayan, Donna Sosnoski, Kazim Kerim Moncal, Yang Wu, Ibrahim T Ozbolat
Despite the recent achievements in cell-based therapies for curing type-1 diabetes (T1D), capillarization in beta (β)-cell clusters is still a major roadblock as it is essential for long-term viability and function of β-cells in vivo. In this research, we report sprouting angiogenesis in engineered pseudo islets (EPIs) made of mouse insulinoma βTC3 cells and rat heart microvascular endothelial cells (RHMVECs). Upon culturing in three-dimensional (3D) constructs under angiogenic conditions, EPIs sprouted extensive capillaries into the surrounding matrix...
February 16, 2018: Biofabrication
Lisa M Rooper, Justin A Bishop, William H Westra
The head and neck is the site of a wide and sometimes bewildering array of neuroendocrine (NE) tumors. Although recognition of NE differentiation may be necessary for appropriate tumor classification and treatment, traditional NE markers such as synaptophysin, chromogranin, and CD56 are not always sufficiently sensitive or specific to make this distinction. Insulinoma-associated protein 1 (INSM1) is a novel transcription factor that has recently demonstrated excellent sensitivity and specificity for NE differentiation in various anatomic sites, but has not yet been extensively evaluated in tumors of the head and neck...
February 12, 2018: American Journal of Surgical Pathology
Liang Zhang, Yuyan Zhao, Lei Guo
17β-estradiol (17β-E2) is a steroid hormone that is known to exert effects on blood glucose homeostasis. The G protein‑coupled estrogen receptor (GPER) has been identified as a non-genomic estrogenic receptor, and is involved in numerous physiological processes, including cell survival, energy provision and metabolism. 17β-E2 may decrease apoptosis by binding to the GPER. The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is involved in physiological and pathological functions such as autophagy...
February 7, 2018: International Journal of Molecular Medicine
Cheng Qi, Jiayue Duan, Qingfeng Shi, Mingguang Wang, Changqing Yan
Insulinomas are functional pancreatic neuroendocrine tumors that cause hypoglycemia and severe morbidity. The aim of our study was to identify gene mutations responsible for tumorigenesis of sporadic insulinoma. Whole exome sequencing analysis was performed on tumors and paired peripheral blood from three patients with insulinomas. After initial analysis, somatic mutations were obtained and a deleterious protein product was further predicted by various bioinformatic programs. Whole exome sequencing identified 55 rare somatic mutations among three insulinoma patients, including MEN1 gene nonsense mutations (c...
February 2018: FEBS Open Bio
Jun Guo, Weiwei Fang, Libo Sun, Yonggang Lu, Lin Dou, Xiuqing Huang, Weiqing Tang, Liqing Yu, Jian Li
Ultraconserved (uc) RNAs, a class of long non-coding RNAs (lncRNAs), are conserved across humans, mice, and rats, but the physiological significance and pathological role of ucRNAs is largely unknown. Here we show that uc.372 is upregulated in the livers of db/db mice, HFD-fed mice, and NAFLD patients. Gain-of-function and loss-of-function studies indicate that uc.372 drives hepatic lipid accumulation in mice by promoting lipogenesis. We further demonstrate that uc.372 binds to pri-miR-195/pri-miR-4668 and suppresses maturation of miR-195/miR-4668 to regulate expression of genes related to lipid synthesis and uptake, including ACC, FAS, SCD1, and CD36...
February 9, 2018: Nature Communications
Chune Liu, Weiwei Zhang, Natia Peradze, Leonie Lang, Jan Straetener, Peter J Feilen, Marcus Alt, Christina Jäger, Katharina Laubner, Nikolaos Perakakis, Jochen Seufert, Günter Päth
Mesenchymal stem cells (MSC) are of interest for cell therapy since their secreted factors mediate immunomodulation and support tissue regeneration. This study investigated the direct humoral interactions between MSC and pancreatic β-cells using human telomerase-immortalized MSC (hMSC-TERT) and rat insulinoma-derived INS-1E β-cells. hMSC-TERT supported survival of cocultured INS-1E β-cells during cellular stress by alloxan (ALX) and streptozotocin (STZ), but not in response to IL-1β. Accordingly, hMSC-TERT had no effect on inflammatory cytokine-related signalling via NF-kB and p-JNK but maintained p-Akt and upregulated p-ERK1/2...
February 5, 2018: Molecular and Cellular Endocrinology
Leah M Wilson, Jessica R Castle
Glycemic control is the mainstay of preventing diabetes complications at the expense of increased risk of hypoglycemia. Severe hypoglycemia negatively impacts the quality of life of patients with type 1 diabetes and can lead to morbidity and mortality. Currently available glucagon emergency kits are effective at treating hypoglycemia when correctly used, however use is complicated especially by untrained persons. Better formulations and devices for glucagon treatment of hypoglycemia are needed, specifically stable liquid glucagon...
February 1, 2018: Journal of Diabetes Science and Technology
Géraldine Blanchard, Maud Marsot, Roselyne Bourassin, Bernard-Marie Paragon, Jean-Jacques Benet, Adeline Linsart
Ferrets have become a common companion animal. But no data are available on the French population of ferrets. The goal of the survey was to characterise this population, including demographic characteristics, husbandry, reported medical care and feeding habits. Complete data were available for 1205 pet ferrets in 709 households. Most ferrets (86·1 %) lived indoors, 1 % received only artificial lighting, and 47 % chewed their cage. For 60 % of the ferrets, body weight was higher in winter and lower in summer...
2018: Journal of Nutritional Science
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