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    Delayed apoptosis allows islet β-cells to implement an autophagic mechanism to promote cell survival.
    PLoS One 2017 17;12(2):e0172567. Epub 2017 Feb 17.
    Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, North Carolina, United States of America.
    Increased β-cell death coupled with the inability to replicate existing β-cells drives the decline in β-cell mass observed in the progression of both major forms of diabetes. Understanding endogenous mechanisms of islet cell survival could have considerable value for the development of novel strategies to limit β-cell loss and thereby promote β-cell recovery. Insulinoma cells have provided useful insight into β-cell death pathways but observations made in cell lines sometimes fail to translate to primary islets. Read More

    Paroxysmal Hypertension Induced by an Insulinoma.
    Intern Med 2017 15;56(4):413-417. Epub 2017 Feb 15.
    Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
    Insulinoma is a rare, usually benign, pancreatic neuroendocrine tumor. The clinical features of an insulinoma are fasting hypoglycemia with neuroglycopenic symptoms including confusion and unusual behavior, while hypertension is usually not associated with the disease. We herein report a patient with insulinoma who manifested paroxysmal hypertension and neuroglycopenic symptoms. Read More

    Effects of Adenoviral Overexpression of Uncoupling Protein-2 and -3 on Mitochondrial Respiration in Insulinoma Cells* * This work was supported by V.A. Medical Research Funds and NIH Grants DK-25295 and HD-29569.
    Endocrinology 2001 Jan;142(1):249-256
    Department of Internal Medicine, Divisions of Endocrinology and Metabolism, University of Iowa and Iowa City Veterans Affairs Medical Center, Iowa City, Iowa 52246.

    Apigenin attenuates streptozotocin-induced pancreatic β cell damage by its protective effects on cellular antioxidant defense.
    In Vitro Cell Dev Biol Anim 2017 Feb 8. Epub 2017 Feb 8.
    Department of Biochemistry, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu, 212013, People's Republic of China.
    Pancreatic beta cells are very sensitive to oxidative stress, which is one of the major causes of cell damages in diabetes. Growing interest has focused on the development of effective therapeutics to protect pancreatic cells from oxidative stress and searching for potentially protective antioxidants for treating diabetes. Apigenin, a plant-derived flavonoid, was investigated to determine whether it could protect rat insulinoma cell lines (RINm5F pancreatic beta cells) against streptozotocin (STZ)-induced oxidative damages and the mechanisms implicated. Read More

    Hepcidin links gluco-toxicity to pancreatic beta cell dysfunction through inhibiting Pdx-1 expression.
    Endocr Connect 2017 Feb 8. Epub 2017 Feb 8.
    T Shu, Department of Central Laboratory, Jiangsu Province Official Hospital, Nanjing, 210024, China
    Objective: Gluco-toxicity is a term used to convey the detrimental effect of hyperglycemia on β-cell function through impaired insulin synthesis. Although it is known that the expression and activity of several key insulin transcription regulators is inhibited, other molecular mechanisms that mediate gluco-toxicity are poorly defined. Our objective was to explore the role of hepcidin in β-cell gluco-toxicity. Read More

    Exo-miR-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress.
    Antioxid Redox Signal 2017 Feb 7. Epub 2017 Feb 7.
    Johns Hopkins University School of Medicine, Pathology , 720 Rutland Avenue , Baltimore, Maryland, United States , 21205 ;
    Aims: Mi(cro)RNAs, one type of non-coding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type-2-diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D. Read More

    Evaluation of the influence of the conjugation site of the chelator agent HYNIC to GLP1 antagonist radiotracer for insulinoma diagnosis.
    Curr Radiopharm 2017 Jan 26. Epub 2017 Jan 26.
    Institute of Energy and Nuclear Research Radiopharmacy Center Av. Prof. Lineu Prestes, 2242 São Paulo,. Brazil.
    Radiotracer diagnosis of insulinoma, can be done using somatostatin or glucagon-like peptide 1 (GLP-1). Performance of GLP-1 antagonists tends to be better than of agonists. We investigated the uptake of the antagonist exendin (9-39), radiolabeled with technetium-99m. Read More

    7, 8-Dihydroxycoumarin (daphnetin) protects INS-1 pancreatic β-cells against streptozotocin-induced apoptosis.
    Phytomedicine 2017 Jan 1;24:119-126. Epub 2016 Dec 1.
    Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, Guangdong 519085, China. Electronic address:
    Background And Objective: Daphnetin (7, 8-dihydroxycoumarin), a natural coumarin compound, is known to exhibit antioxidant and anti-inflammatrory effects. However, the underlying mechanisms of its anti-apoptotic and antidiabetic effects yet not been examined. Therefore, the present work studied the anti-apoptotic and anti-diabetic effects of daphnetin by in vitro experiments. Read More

    Endoscopic Radiofrequency Ablation of the Pancreas.
    Dig Dis Sci 2017 Feb 3. Epub 2017 Feb 3.
    Department of Internal Medicine, Waterbury Hospital, Waterbury, CT, USA.
    Radiofrequency ablation (RFA) is a well-established technique to ablate dysplastic and neoplastic tissue via local thermal coagulative necrosis. Despite the widespread use in management of several cancers, the application of RFA in pancreas has been limited due to the increased risks of complications from the increased sensitivity of pancreatic tissue to thermal injury and proximity to vascular and biliary structures. RFA has been successfully used during laparotomy for locally advanced pancreatic carcinoma but requires an invasive approach. Read More

    Resection of postoperative liver metastasis from pancreatic neuroendocrine tumors: report of one case.
    Transl Gastroenterol Hepatol 2016 1;1:47. Epub 2016 Jun 1.
    Department of Abdominal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, National Cancer Center of China, Beijing 100021, China.
    Pancreatic neuroendocrine tumor (pNET) is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. Except insulinoma, majority of pNET are metastatic when diagnosis. Read More

    68Ga-Exendin-4 PET/CT in Evaluation of Endoscopic Ultrasound-Guided Ethanol Ablation of an Insulinoma.
    Clin Nucl Med 2017 Jan 27. Epub 2017 Jan 27.
    From the Departments of *Nuclear Medicine, †Gastroenterology, and ‡Endocrinology, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing, China.
    A 32-year-old man with endogenous hyperinsulinemic hypoglycemia was clinically diagnosed with an insulinoma. Conventional imaging result was negative, and a previous exploratory laparotomy with distal pancreatectomy failed to detect the tumor. Ga-exendin-4 PET/CT showed a lesion with intense radioactivity in the head of the pancreas suggestive of an insulinoma, and endoscopic ultrasound-guided ethanol ablation was performed. Read More

    [Multiple Endocrine Neoplasia Type 1(MEN1)Presenting with Hypoglycemic Attacks - A Case Report].
    Gan To Kagaku Ryoho 2016 Nov;43(12):2196-2198
    Dept. of Surgery, Kobe Ekisaikai Hospital.
    A woman in her 60s visited our hospital because of frequent hypoglycemia and episodes of unconsciousness over the last 6 years. A 4 cm tumor was detected on the pancreatic tail using abdominal computed tomography and ultrasonography. An insulinoma was strongly suspected from the results of the fasting test and glucagon load test, and a distal pancreatectomy with splenectomy was performed. Read More

    Coupling of Insulin Secretion and Display of a Granule-resident Zinc Transporter ZnT8 on the Surface of Pancreatic beta-Cells.
    J Biol Chem 2017 Jan 27. Epub 2017 Jan 27.
    Johns Hopkins School of Medicine, United States
    The islet-specific zinc transporter ZnT8 mediates zinc enrichment in the insulin secretory granules of the pancreatic beta cell. This granular zinc transporter is also a major self-antigen found in type-1 diabetes (T1D) patients. It is not clear whether ZnT8 can be displayed on the cell surface and how insulin secretion may regulate the level of ZnT8 exposure to extracellular immune surveillance. Read More

    Sporadic insulinomas on volume perfusion CT: dynamic enhancement patterns and timing of optimal tumour-parenchyma contrast.
    Eur Radiol 2017 Jan 20. Epub 2017 Jan 20.
    Department of Radiology, Peking Union Medical College Hospital, Shuaifuyuan No.1, Dongcheng District, Beijing, China.
    Objectives: To assess enhancement patterns of sporadic insulinomas on volume perfusion CT (VPCT), and to identify timing of optimal tumour-parenchyma contrast.

    Methods: Consecutive patients who underwent VPCT for clinically suspected insulinomas were retrospectively identified. Patients with insulinomas confirmed by surgery were included, and patients with familial syndromes were excluded. Read More

    Sirtuin 1 independent effects of resveratrol in INS-1E β-cells.
    Chem Biol Interact 2017 Feb 17;264:52-60. Epub 2017 Jan 17.
    Department of Science and Environment, Roskilde University, Roskilde, Denmark. Electronic address:
    Resveratrol (Resv), a natural polyphenol, is suggested to have various health benefits including improved insulin sensitivity. Resv activates Sirtuin (Sirt1) in several species and tissues. Sirt1 is a protein deacetylase with an important role in ageing, metabolism and β-cell function. Read More

    Radioiodinated Exendin-4 Is Superior to the Radiometal-Labelled Glucagon-Like Peptide-1 Receptor Probes Overcoming Their High Kidney Uptake.
    PLoS One 2017 19;12(1):e0170435. Epub 2017 Jan 19.
    Department of Nuclear Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.
    GLP-1 receptors are ideal targets for preoperative imaging of benign insulinoma and for quantifying the beta cell mass. The existing clinical tracers targeting GLP-1R are all agonists with low specific activity and very high kidney uptake. In order to solve those issues we evaluated GLP-1R agonist Ex-4 and antagonist Ex(9-39) radioiodinated at Tyr40 side by side with [Nle14,Lys40(Ahx-DOTA-68Ga)NH2]Ex-4 (68Ga-Ex-4) used in the clinic. Read More

    Development of (111)In-labeled exendin(9-39) derivatives for single-photon emission computed tomography imaging of insulinoma.
    Bioorg Med Chem 2017 Feb 3;25(4):1406-1412. Epub 2017 Jan 3.
    Department of Patho-Functional Bioanalysis, Kyoto University Graduate School of Pharmaceutical Sciences, 46-29, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address:
    Insulinoma is a tumor derived from pancreatic β-cells, and the resulting hyperinsulinemia leads to characteristic hypoglycemia. Recent studies have reported the frequent overexpression of glucagon-like peptide-1 receptor (GLP-1R) in human insulinomas, suggesting that the binding of a radiolabeled compound to GLP-1R is useful for the imaging of such tumors. Exendin(9-39), a fragment peptide of exendin-3 and -4, binds GLP-1R with high affinity and acts as an antagonist. Read More

    Quantitative proteomic profiling of the extracellular matrix of pancreatic islets during the angiogenic switch and insulinoma progression.
    Sci Rep 2017 Jan 10;7:40495. Epub 2017 Jan 10.
    David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, U.S.A.
    The angiogenic switch, the time at which a tumor becomes vascularized, is a critical step in tumor progression. Indeed, without blood supply, tumors will fail to grow beyond 1 mm(3) and are unlikely to disseminate. The extracellular matrix (ECM), a major component of the tumor microenvironment, is known to undergo significant changes during angiogenesis and tumor progression. Read More

    REST corepressors RCOR1 and RCOR2 and the repressor INSM1 regulate the proliferation-differentiation balance in the developing brain.
    Proc Natl Acad Sci U S A 2017 Jan 3;114(3):E406-E415. Epub 2017 Jan 3.
    Vollum Institute, Oregon Health and Science University, Portland, OR 97239;
    The transcriptional events that lead to the cessation of neural proliferation, and therefore enable the production of proper numbers of differentiated neurons and glia, are still largely uncharacterized. Here, we report that the transcription factor Insulinoma-associated 1 (INSM1) forms complexes with RE1 Silencing Transcription factor (REST) corepressors RCOR1 and RCOR2 in progenitors in embryonic mouse brain. Mice lacking both RCOR1 and RCOR2 in developing brain die perinatally and generate an abnormally high number of neural progenitors at the expense of differentiated neurons and oligodendrocyte precursor cells. Read More

    Scaling it down: new in vitro tools to get the balance right.
    Biochem J 2017 Jan;474(1):47-50
    Metabolic Research Laboratories, Wellcome Trust/MRC Institute of Metabolic Science & MRC Metabolic Diseases Unit, Addenbrooke's Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, U.K.
    Treatments for diabetes and obesity based on enteroendocrine hormones are a focus of research interest, partly due to the successes of glucagon-like peptide-1 (GLP-1) mimetic peptides in the treatment of diabetes and the correlation of altered enteroendocrine profiles with the positive metabolic outcomes of gastric bypass surgery. It is thought that simultaneous stimulation of more than one receptor might mimic the superior efficacy of the latter and dual or triple-agonist peptides are under investigation. An important step in developing multiple agonists is to establish the relative pharmacological potency and efficacy of new molecules at its different target receptors, and to optimise the balance of activities to achieve the desired treatment outcome. Read More

    Hepatic Steatosis: Etiology, Patterns, and Quantification.
    Semin Ultrasound CT MR 2016 Dec 12;37(6):501-510. Epub 2016 Aug 12.
    Liver Imaging Team, Department of Radiology, School of Medicine, Hacettepe University, Ankara, Turkey. Electronic address:
    Hepatic steatosis can occur because of nonalcoholic fatty liver disease (NAFLD), alcoholism, chemotherapy, and metabolic, toxic, and infectious causes. Pediatric hepatic steatosis is also becoming more frequent and can have distinctive features. The most common pattern is diffuse form; however, it can present in heterogenous, focal, multinodular, perilesional, perivascular, subcapsular, and lobar forms. Read More

    A Clinicopathological Study of Malignant Insulinoma in a Contemporary Series.
    Pancreas 2017 Jan;46(1):48-56
    From the *Division of Endocrinology, Cedars-Sinai Medical Center; †Division of Endocrinology, UCLA David Geffen School of Medicine, ‡Department of Surgery, §Division of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, CA; ∥Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; ¶Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China; and #Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA.
    Objective: The aim of the study was to address the origin and natural history of malignant insulinoma.

    Methods: Retrospective review of medical records of patients diagnosed with insulinoma at Cedars-Sinai Medical Center between 2000 and 2015 was conducted. Hormonal expression in tumor specimens was examined by immunostaining. Read More

    EX4 stabilizes and activates Nrf2 via PKCδ, contributing to the prevention of oxidative stress-induced pancreatic beta cell damage.
    Toxicol Appl Pharmacol 2017 Jan 7;315:60-69. Epub 2016 Dec 7.
    College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-ku, Incheon, South Korea; Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-ku, Incheon, South Korea; Gachon Medical Research Institute, Gil Hospital, Incheon, South Korea. Electronic address:
    Oxidative stress in pancreatic beta cells can inhibit insulin secretion and promote apoptotic cell death. Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, can suppress beta cell apoptosis, improve beta cell function and protect against oxidative damage. In this study, we investigated the molecular mechanisms for antioxidative effects of EX4 in pancreatic beta cells. Read More

    Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog.
    Endocrinol Diabetes Metab Case Rep 2016 17;2016. Epub 2016 Nov 17.
    Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medicine, Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan.
    : Insulin antibodies (IA) associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA) found in insulin autoimmune syndrome (IAS), which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Read More

    Insulinoma Detection With MDCT: Is There a Role for Whole-Pancreas Perfusion?
    AJR Am J Roentgenol 2017 Feb 8;208(2):306-314. Epub 2016 Dec 8.
    2 Department of General Surgery, Peking Union Medical College Hospital, Beijing, China.
    Objective: The purpose of this study is to investigate the role of whole-pancreas perfusion in detecting insulinomas with the use of MDCT.

    Materials And Methods: From January 2011 to December 2011, a total of 70 consecutive patients (33 men and 37 women; mean age, 46 years; range, 17-73 years) who underwent biphasic contrast-enhanced CT and whole-pancreas CT perfusion for suspected insulinomas were identified retrospectively. Patients were monitored for at least 3 years. Read More

    Coordinated activation of mitochondrial respiration and exocytosis mediated by PKC signaling in pancreatic β-cells.
    FASEB J 2016 Dec 7. Epub 2016 Dec 7.
    Mitochondrial Function, Nestlé Institute of Health Sciences, Lausanne, Switzerland;
    Mitochondria play a central role in pancreatic β-cell nutrient sensing by coupling their metabolism to plasma membrane excitability and insulin granule exocytosis. Whether non-nutrient secretagogues stimulate mitochondria as part of the molecular mechanism to promote insulin secretion is not known. Here, we show that PKC signaling, which is employed by many non-nutrient secretagogues, augments mitochondrial respiration in INS-1E (rat insulinoma cell line clone 1E) and human pancreatic β-cells. Read More

    A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix: Analysis of 37 cases.
    Gynecol Oncol 2017 Feb 28;144(2):384-390. Epub 2016 Nov 28.
    Division of Pathology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
    Objective: High-grade neuroendocrine carcinoma of uterine cervix (HGNCUC) has been recognized as a highly malignant tumor. Therapeutic strategy specific to neuroendocrine (NE) tumors needs to be considered, but some cases wouldn't allow simple final diagnoses. Insulinoma-associated protein 1 (INSM1), which is a zinc-finger transcription factor related to NE differentiation, is frequently expressed in NE tumors. Read More

    Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) in insulinomas: Indications and clinical relevance in a single investigator cohort of 47 patients.
    Endocrine 2016 Nov 30. Epub 2016 Nov 30.
    Division of Endocrinology & Diabetology, Philipp's University and University Hospital, Marburg, Hessia, Germany.
    Purpose: This study was aimed to investigate the role and relevance of endoscopic ultrasound-guided fine-needle aspiration biopsy in the diagnostic work-up of insulinomas.

    Methods: We have analysed the frequency, clinical indications, success rate (obtaining diagnostic tissue), diagnostic accuracy (in comparison to the pathological diagnosis after surgery), complications, and tolerability of endoscopic ultrasound-guided fine-needle aspiration biopsy and the localization and size of the lesions in 47 consecutive patients (29 females, 18 males; 46 ± 15 years) who had surgery for insulinoma following fasting test and were explored by single investigator EUS 1994-2015.

    Results: Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed in 21 % (10/47) of the patients. Read More

    Incomplete Re-Expression of Neuroendocrine Progenitor/Stem Cell Markers is a Key Feature of β-Cell Dedifferentiation.
    J Neuroendocrinol 2017 Jan;29(1)
    Harry Perkins Institute of Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, Australia.
    There is increasing evidence to suggest that type 2 diabetes mellitus (T2D), a pandemic metabolic disease, may be caused by β-cell dedifferentiation (βCD). However, there is currently no universal definition of βCD, and the underlying mechanism is poorly understood. We hypothesise that a high-glucose in vitro environment mimics hyperglycaemia in vivo and that β cells grown in this milieu over a long period will undergo dedifferentiation. Read More

    Ferret Oncology: Diseases, Diagnostics, and Therapeutics.
    Vet Clin North Am Exot Anim Pract 2017 Jan;20(1):183-208
    Faculty of Veterinary Medicine, Division of Zoological Medicine, Department of Clinical Sciences of Companion Animals, Utrecht University, Yalelaan 108, Utrecht 3584 CM, The Netherlands. Electronic address:
    Neoplastic disease is common in ferrets. Approximately half of all tumors diagnosed in ferrets are located in the endocrine or hemolymphatic system. Many factors may influence the choice of treatment. Read More

    Insulinoma or non-insulinoma pancreatogenous hypoglycemia? A diagnostic dilemma.
    J Surg Case Rep 2016 Nov 24;2016(11). Epub 2016 Nov 24.
    Department of Surgery, University of Alberta, Edmonton, Canada
    Insulinoma is the most common cause of endogenous hyperinsulinemic hypoglycemia in adults. An alternate etiology, non-insulinoma pancreatogenous hypoglycemia (NIPH), is rare. Clinically, NIPH is characterized by postprandial hyperinsulinemic hypoglycemia, negative 72-h fasts, negative preoperative localization studies for insulinoma and positive selective arterial calcium infusion tests. Read More

    Double pancreatic tumors in an adolescent: Imaging features.
    Pediatr Int 2016 Nov;58(11):1239-12342
    Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan.
    Insulinoma is generally identified as a single tumor and seldom occurs in children or adolescents. A 14-year-old girl with difficulty in waking was found to have hyperinsulinemic hypoglycemia. On abdominal ultrasonography two hypoechoic masses (8 and 12 mm in diameter) were seen in the pancreatic body: the larger mass was hypervascular, whereas the smaller one was hypovascular. Read More

    Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application.
    BMC Biotechnol 2016 Nov 24;16(1):84. Epub 2016 Nov 24.
    Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto de Estudios de la Inmunidad Humoral "Prof. Ricardo A. Margni" (IDEHU), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
    Background: The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A). Read More

    Imaging of secretory tumors of the gastrointestinal tract.
    Abdom Radiol (NY) 2016 Nov 23. Epub 2016 Nov 23.
    Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Houston, TX, 77030, USA.
    Gastrointestinal secretory tumors, or gastroenteropancreatic neuroendocrine tumors, encompass a wide array of endocrine cell tumors. The significance of these tumors lies in their ability to alter physiology through hormone production as we well as in their malignant potential. Functioning tumors may present earlier due to symptomatology; conversely, non-functioning tumors are often diagnosed late as they reach large sizes, causing symptoms secondary to local mass effect. Read More

    P-selectin-mediated LOX expression promotes insulinoma growth in Rip1-Tag2 mice by increasing tissue stiffness.
    Int J Biol Sci 2016 18;12(11):1289-1297. Epub 2016 Oct 18.
    Department of Gastrointestinal Surgery, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510630, China.
    P-selectin, a cell adhesion molecule, is an important member of the selectin family. Recent studies have shown that P-selectin deletion inhibits tumor growth in Rip1-Tag2 mice by suppressing platelet accumulation in tumor tissues. This study aimed to evaluate whether and how P-selectin affects tumor stiffness in Rip1-Tag2 mice. Read More

    Noninvasive assessment of tissue-engineered graft viability by oxygen-17 magnetic resonance spectroscopy.
    Biotechnol Bioeng 2016 Nov 21. Epub 2016 Nov 21.
    Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota, 2021 Sixth Street SE, Minneapolis, Minnesota, 55455.
    Transplantation of macroencapsulated tissue-engineered grafts (TEGs) is being investigated as a treatment for type 1 diabetes, but there is a critical need to measure TEG viability both in vitro and in vivo. Oxygen deficiency is the most critical issue preventing widespread implementation of TEG transplantation and delivery of supplemental oxygen (DSO) has been shown to enhance TEG survival and function in vivo. In this study, we demonstrate the first use of oxygen-17 magnetic resonance spectroscopy ((17) O-MRS) to measure the oxygen consumption rate (OCR) of TEGs and show that in addition to providing therapeutic benefits to TEGs, DSO with (17) O2 can also enable measurements of TEG viability. Read More

    Giant insulinoma: report of a case and review of published reports.
    Surg Case Rep 2016 Dec 19;2(1):136. Epub 2016 Nov 19.
    Department of Surgery, Hitachi General Hospital, 2-1-1 Jonan-cho, Hitachi, Ibaraki, 317-0077, Japan.
    Background: Larger insulinomas are reportedly more likely to be malignant; however, their biological behavior has not been clearly elucidated. We here report the characteristics and treatment of a giant insulinoma with local invasion and lymph node metastasis. We also review published reports concerning the clinical features of giant insulinomas and comparing their grading with that of pancreatic neuroendocrine tumors. Read More

    Operation for insulinomas in multiple endocrine neoplasia type 1: When pancreatoduodenectomy is appropriate.
    Surgery 2017 Mar 15;161(3):727-734. Epub 2016 Nov 15.
    Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
    Background: Distal pancreatectomy is the most frequent operation for insulinomas complicating multiple endocrine neoplasia type 1 insulinoma, although there are conditions for which a different operative approach might be preferable. In this article, we report the operative experience of a referral center for multiple endocrine neoplasia type 1 insulinoma.

    Methods: Twelve patients underwent operations between 1992 and 2015: 8 underwent a distal pancreatic resection, and 4 underwent a pancreatoduodenectomy. Read More

    Role of CCN5 (WNT1 inducible signaling pathway protein 2) in pancreatic islets.
    J Diabetes 2016 Nov 12. Epub 2016 Nov 12.
    Department of Pathology, The Research Institute of McGill University Health Centre, Montreal, Canada.
    In search of direct targets of insulin-like growth factor (IGF)-1 action, we discovered CCN5 (WNT1 inducible signaling pathway protein 2 [WISP2]) as a novel protein expressed in pancreatic β-cells. As a member of the "CCN" ( C ysteine-rich angiogenic inducer 61 [Cyr61], C onnective tissue growth factor [CTGF in humans], and N ephroblastoma overexpressed [Nov; in chickens]) family, the expression of CCN5/WISP2 is stimulated by IGF-1 together with Wnt signaling. When overexpressed in insulinoma cells, CCN5 promotes cell proliferation and cell survival against streptozotocin-induced cell death. Read More

    Arachidonic acid and lipoxin A4 attenuate alloxan-induced cytotoxicity to RIN5F cells in vitro and type 1 diabetes mellitus in vivo.
    Biofactors 2016 Nov 15. Epub 2016 Nov 15.
    Department of Medicine, BioScience Research Centre, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam, 530048, India.
    Objective: We studied whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5F) cells against alloxan-induced apoptosis in vitro and type 1 diabetes mellitus (type 1 DM) in vivo and if so, mechanism of this beneficial action.

    Material And Methods: In vitro study was conducted using RIN5F cells while in vivo study was performed in Wistar rats. The effect of PUFAs, cyclo-oxygenase and lipoxygenase inhibitors, various eicosanoids and PUFAs metabolites: lipoxin A4 (LXA4), resolvin D2 and protectin against alloxan-induced cytotoxicity to RIN5F cells and type 1 DM was studied. Read More

    The Rip1Tag2 Transgenic Mouse Model.
    Methods Mol Biol 2016 ;1464:151-161
    Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058, Basel, Switzerland.
    The Rip1Tag2 transgenic mouse model of β-cell carcinogenesis has been instrumental in studying various aspects of tumor angiogenesis and in investigating the response to anti-angiogenic therapeutics. Thereby, the in-depth assessment of blood and lymphatic vessel phenotypes and functionality represents key experimental analyses. In this chapter, we describe basic protocols to assess tumor blood vessel morphology (pericyte coverage), functionality (perfusion, leakiness, and hypoxia), lymphatic tumor coverage, and tumor cell proliferation and apoptosis based on immunofluorescence microscopy analysis. Read More

    CXCL12 protects pancreatic β-cells from oxidative stress by a Nrf2-induced increase in catalase expression and activity.
    Proc Jpn Acad Ser B Phys Biol Sci 2016 ;92(9):436-454
    Department of Molecular Biology, Institute for Biological Research, University of Belgrade.
    Due to intrinsically low levels of antioxidant enzyme expression and activity, insulin producing pancreatic β-cells are particularly susceptible to free radical attack. In diabetes mellitus, which is accompanied by high levels of oxidative stress, this feature of β-cells significantly contributes to their damage and dysfunction. In light of the documented pro-survival effect of chemokine C-X-C Ligand 12 (CXCL12) on pancreatic β-cells, we examined its potential role in antioxidant protection. Read More

    Clinical characteristics and management of insulin-producing neuroendocrine carcinomas.
    Acta Gastroenterol Belg 2016 Jul-Sep;79(2):321-327
    Background And Aims: Due to rarity of insulin-producing pancreatic neuroendocrine carcinomas, no large, nor randomized studies of the clinical course, treatment options and outcome are available. Therefore, we want to share our personal experience and we retrospectively reviewed a cohort of five patients.

    Patients And Methods: This study reports on the clinical characteristics, disease course, management and outcome of five patients with an advanced pancreatic neuroendocrine carcinoma with insulin production, which we followed recently in our center (between 2006 and 2015). Read More

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