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  • 1.
    Anthony, Lowell
    et al.
    Univ Kentucky, Lexington, KY USA..
    Hoersch, Dieter
    Zentralklin Bad Berka, Bad Berka, Germany..
    Ervin, Claire
    RTI Hlth Solut, Res Triangle Pk, NC USA..
    Kulke, Matthew H.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Pavel, Marianne
    Charite, D-13353 Berlin, Germany..
    Bergsland, Emily
    UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA..
    Caplin, Martyn
    Royal Free Hosp, Pond St, London NW3 2QG, England..
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Warner, Richard
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA..
    Kunz, Pamela
    Stanford Univ, Palo Alto, CA 94304 USA..
    Metz, David C.
    Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Pasieka, Janice
    Tom Baker Canc Ctr Calgary, Calgary, AB, Canada..
    Pavlakis, Nick
    Royal N Shore Hosp, St Leonards, NSW 2065, Australia..
    DiBenedetti, Dana
    RTI Hlth Solut, Res Triangle Pk, NC USA..
    Haydysch, Emily
    RTI Hlth Solut, Res Triangle Pk, NC USA..
    Yang, Qi Melissa
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Jackson, Shanna
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Arnold, Karie
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Law, Linda
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Assessing Treatment Benefit of Telotristat Etiprate in Patients with Carcinoid Syndrome: Patient Exit Interviews2016In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 45, no 3, 470-470 p.Article in journal (Other academic)
  • 2.
    Anvari, Ebrahim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fred, Rikard G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The H-1-Receptor Antagonist Cetirizine Protects Partially Against Cytokine- and Hydrogen Peroxide-Induced beta-TC6 Cell Death In Vitro2014In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 43, no 4, 624-629 p.Article in journal (Refereed)
    Abstract [en]

    Objective It has been proposed that the histamine 1 (H-1) receptor not only promotes allergic reactions but also modulates autoimmune diseases, such as type 1 diabetes. In line with this, it has recently been reported that the H-1-receptor antagonist cetirizine can counteract the activation of signals/factors pertinent to the pathogenesis of type 1 diabetes and cytokine-induced beta-cell destruction. Therefore, the overall aim of this study was to determine whether H-1-receptor antagonists affect cytokine-induced beta-cell death and signaling in vitro. Methods The insulin-producing cell line beta-TC6 was exposed to the proinflammatory cytokines interleukin 1 beta(+) interferon gamma, or hydrogen peroxide. The H-1-receptor antagonists desloratadine and cetirizine were added to the cell cultures and cell viability; macrophage inhibitory factor levels, c-Jun N-terminal kinase phosphorylation, c-Jun expression, and beta-catenin levels were analyzed by flow cytometry, real-time polymerase chain reaction, and immunoblotting. Results Cetirizine protected partially against both cytokine- and hydrogen peroxide-induced cell death. This effect was paralleled by an inhibition of cytokine-induced c-Jun N-terminal kinase phosphorylation, c-Jun induction, and a restoration of macrophage inhibitory factor contents. Cetirizine also increased the beta-TC6 cell contents of beta-catenin at basal conditions. Conclusions Our results indicate a protective effect of a specific H-1-receptor antagonist.

  • 3.
    Barbu, Andreea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Bodin, Bbirgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Källskog, Örjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Sandberg, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Börjesson, Joey Lau
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Blood flow in endogenous and transplanted pancreatic islets in anesthetized rats: Effects of lactate and pyruvate2012In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 41, no 8, 1263-1271 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The objective of this study was to evaluate the effects of exogenously administered lactate and pyruvate on blood perfusion in endogenous and transplanted islets. METHODS: Anesthetized Wistar-Furth rats were given lactate or pyruvate intravenously, and regional blood perfusion was studied 3 or 30 minutes later with a microsphere technique. Separate rats received a 30-minute infusion of pyruvate or lactate into the portal vein before blood flow measurements. We also administered these substances to islet-implanted rats 4 weeks after transplantation and measured graft blood flow with laser Doppler flowmetry. The expression of monocarboxylate transporter 1 and lactate dehydrogenase A was analyzed. RESULTS: The expression of monocarboxylate transporter 1 and lactate dehydrogenase A was markedly up-regulated in transplanted as compared with endogenous islets. Administration of pyruvate, but not lactate, increased mesenteric blood flow after 3 minutes. Pyruvate decreased mesenteric blood flow after 30 minutes, whereas lactate decreased only islet blood flow. These responses were absent in transplanted animals. A continuous intraportal infusion of lactate or pyruvate increased selectively islet blood flow but did not affect blood perfusion of transplanted islets. CONCLUSIONS: Lactate and pyruvate affect islet blood flow through effects mediated by interactions between the liver and the nervous system. Such a response can help adjust the release of islet hormones during excess substrate concentrations.

  • 4.
    Barbu, Andreea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Lejonklou, Margareta H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Progranulin Stimulates Proliferation of Mouse Pancreatic Islet Cells and Is Overexpressed in the Endocrine Pancreatic Tissue of an MEN1 Mouse Model2016In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 45, no 4, 533-540 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Progranulin (PGRN) promotes cell growth and cell cycle progression in several cell types and contributes to tumorigenesis in diverse cancers. We have recently reported PGRN expression in islets and tumors developed in an MEN1 transgenic mouse. Here we sought to investigate PGRN expression and regulation after exposure to hypoxia as well as its effects on pancreatic islet cells and neuroendocrine tumors (NETs) in MEN1 mice.

    METHODS: Gene and protein expression were analyzed by quantitative polymerase chain reaction, immunohistochemistry, and Western blot. We also investigated PGRN expression in samples from patients carrying pancreatic NETs associated or not with the multiple endocrine neoplasia 1 syndrome, using enzyme-linked immunosorbent assay and immunohistochemistry analysis.

    RESULTS: Progranulin is upregulated in tumors and islets of the MEN1 mouse as well as in the serum of patients with pancreatic NETs associated with glucagonoma syndrome. In normal mice islets and pancreatic tumors, PGRN expression was strongly potentiated by hypoxia. Progranulin promotes cell proliferation in islet cells and βTC-6 cells, a process paralleled by activation of the mitogen-activated protein kinase signaling cascade.

    CONCLUSIONS: Our findings identify PGRN as an effective inducer of pancreatic islet cell proliferation and a possible important factor for pancreatic endocrine tumor development.

  • 5.
    Bergström, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Cui, Tao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Li, Su-Chen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Nystrand, Mats
    Giandomenico, Valeria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Microarray Immunoassay Development to Specifically Detect Autoantibodies in Small Intestine Neuroendocrine Tumor (SI-NET) Patients2013In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, no 2, 369-370 p.Article in journal (Other academic)
  • 6.
    Crona, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Antonodimitrakis, Pantelis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrin Oncology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Multiple and Secondary Hormone Secretion in Patients With Metastatic Pancreatic Neuroendocrine Tumors2017In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 3, 441-441 p.Article in journal (Other academic)
  • 7.
    Cui, Tao
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tsolakis, Apostolos V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Li, Su-Chen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Giandomenico, Valeria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Olfactory Receptor 51E1 is a Potential Novel Tissue Biomarker for the Diagnosis of Small Intestine Neuroendocrine Tumors2013In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, no 2, 373-373 p.Article in journal (Other academic)
  • 8.
    Frisk, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tallkvist, Jonas
    Gadhasson, Inga-Lill
    Blomberg, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Friman, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Ilbäck, Nils-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Coxsackievirus B3 infection affects metal-binding/transporting proteins and trace elements in the pancreas in mice2007In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 35, no 3, e37-e44 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The trigger of juvenile diabetes has been suggested to be an interaction between a virus and trace elements, where enteroviruses, including coxsackievirus B3 (CVB3), have been discussed as potential initiators. The aim of this study was to investigate the effects in the pancreas on gene expressions of metallothionein 1 (MT1), divalent metal transporter 1 (DMT1), and zinc transporter 5 (ZnT-5) and concomitant changes in iron (Fe), copper (Cu), and zinc (Zn) in serum and pancreas of Balb/c mice on days 3, 6, and 9 of CVB3 infection. Methods: Trace elements were measured through inductively coupled plasma-mass spectrometry, and CVB3, MT1, DMT1, and ZnT-5 were measured by reverse transcription/polymerase chain reaction. Results: Virus was found in the pancreas on all days, with a peak on day 3. Infection tended to increase Fe in both serum and the pancreas. The Cu/Zn ratio in the pancreas increased early in the infection because of a great decrease in Zn. In serum, the Cu/Zn ratio was not increased until day 9 of the disease. In the pancreas, MT1 decreased, whereas DMT1 tended to increase on day 6, and ZnT-5 increased progressively during the course of the disease. Conclusions: Virus-induced changes in trace elements, MT1, DMT1, and ZnT-5 in the pancreas may reflect early stages of the development of pancreatitis and prestages of diabetic disease.

  • 9.
    Gylfe, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Grapengiesser, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dansk, Heléne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Hellman, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The Neurotransmitter ATP Triggers Ca2+ Responses Promoting Coordination of Pancreatic Islet Oscillations2012In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 41, no 2, 258-263 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: Pulsatile insulin release into the portal vein is critically dependent on entrainment of the islets in the pancreas into a common oscillatory phase. Because the pulses reflect periodic variations of the cytoplasmic Ca2+ concentration ([Ca2+](i)), we studied whether the neurotransmitters adenosine triphosphate (ATP) and acetylcholine promote synchronization of [Ca2+](i) oscillations between islets lacking contact.

    Methods: Medium-sized and small mouse islets and cell aggregates were used for measuring [Ca2+](i) with the indicator fura-2.

    Results: Exposure to acetylcholine resulted in an initial [Ca2+](i) peak followed by disappearance of the [Ca2+](i) oscillations induced by 11-mmol/L glucose. The effect of ATP was often restricted to an elusive [Ca2+](i) peak. The incidence of distinct [Ca2+](i) responses to ATP increased under conditions (accelerated superfusion, small islets, or cell aggregates) intended to counteract purinoceptor desensitization owing to intercellular accumulation of ATP. Attempts to imitate neural activity by brief (15 seconds) exposure to ATP or acetylcholine resulted in temporary synchronization of the glucose-induced [Ca2+](i) oscillations between islets lacking contact.

    Conclusions: The data support the idea that purinergic signaling has a key role for coordinating the oscillatory activity of the islets in the pancreas, reinforcing previous arguments for the involvement of nonadrenergic, noncholinergic neurons.

  • 10.
    Hellman, Bo
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Dansk, Heléne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Grapengiesser, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sulfonylurea blockade of KATP channels unmasks a distinct type of glucose-induced Ca2+ decrease in pancreatic β-cells2017In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 4, 467-475 p.Article in journal (Refereed)
    Abstract [en]

    Objectives: This study aimed to explore how sulfonylurea blockade of K-ATP channels affects the early Ca2+ signals for glucose generation of insulin release. Methods: Cytoplasmic Ca2+ was measured with ratiometric microfluorometry in isolated mouse islets loaded with Fura-PE3. Results: After sulfonylurea blockade of the K-ATP channels (50 mu M-1 mM tolbutamide or 1 mu M-1 mM gliclazide), increase of glucose from 3 to 20 mM resulted in suppression of elevated Ca2+ during a 3- to 5-minute period. The Ca2+ decrease was shorter after inhibition of the Na/K pump with ouabain (10 and 100 mu M) but prolonged when the alpha(2A) adrenoceptors were activated with clonidine (1 and 10 nM) or epinephrine (10 nM). Inhibition of the sarco/endoplasmic reticulum Ca2+-ATPase pump with 10 mu M cyclopiazonic acid counteracted the action of 10 nM clonidine, making the Ca2+ decrease shorter than in controls. Extended superfusion of islets with a medium containing 20 mM glucose and 1 mM tolbutamide sometimes resulted in delayed appearance of Ca2+ oscillations mediated by periodic interruption of elevated Ca2+. Conclusions: Increase of glucose generates prompt suppression of cytoplasmic Ca2+ in beta-cells lacking functional KATP channels. Activation of alpha(2A) adrenoceptors markedly prolongs the period of glucose-induced Ca2+ decrease, an effect counteracted by cyclopiazonic acid.

  • 11.
    Krishnan, Kalaiselvan
    et al.
    Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden..
    Ma, Zuheng
    Karolinska Univ Hosp Solna, Dept Mol Med & Surg, Stockholm, Sweden..
    Bjoerklund, Anneli
    Karolinska Univ Hosp Solna, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Endocrinol Metab & Diabet, Stockholm, Sweden..
    Islam, Md. Shahidul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Soder Sjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden..
    Calcium Signaling in a Genetically Engineered Human Pancreatic beta-Cell Line2015In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 44, no 5, 773-777 p.Article in journal (Refereed)
    Abstract [en]

    Objectives The use of primary human -cells for studying Ca2+ signaling is limited by the scarcity of human pancreatic islets. Rodent insulinoma cell lines are widely used, but it is difficult to extrapolate results obtained from rodent cells to human. Recently, a genetically engineered human -cell line EndoC-BH1 has been developed. We have examined whether the EndoC-BH1 cells could be used as a model for studying Ca2+ signaling in the -cells. Methods We used microscope-based fluorometry to measure cytoplasmic-free Ca2+ concentration from fura-2-loaded single EndoC-BH1 cells cultured on glass cover slips. Ca2+ responses to different agonists of insulin secretion were studied. Insulin secretion was measured by radioimmunoassay. Results EndoC-BH1 cells secreted insulin in response to glucose in a dose-dependent manner, and the secretion was enhanced by GLP-1 (glucagon-like peptide 1). Glucose, potassium chloride, carbachol, l-arginine, and tolbutamide increased cytoplasmic-free Ca2+ concentration in the EndoC-BH1 cells. We found that GLP-1 was essential for Ca2+ response to glucose and tolbutamide. Conclusions We concluded that the EndoC-BH1 cells can be used as model cells to study Ca2+ signaling and stimulus-secretion coupling in the human -cells.

  • 12.
    Krishnan, Kalaiselvan
    et al.
    Karolinska Institutet.
    Ma, Zuheng
    Bjorklund, Anneli
    Islam, Md. Shahidul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Role of Transient Receptor Potential Melastatin-like Subtype 5 Channel in Insulin Secretion From Rat beta-Cells2014In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 43, no 4, 597-604 p.Article in journal (Refereed)
    Abstract [en]

    Objective Several studies have reported that the transient receptor potential melastatin-like subtype 5 (TRPM5) channel, a Ca2+-activated monovalent cation channel, is involved in the stimulus-secretion coupling in the mouse pancreatic beta-cells. We have studied the role of the TRPM5 channel in regulating insulin secretion and cytoplasmic free Ca2+ concentration ([Ca2+](i)) in the rat beta-cells by using triphenylphosphine oxide, a selective inhibitor of the channel. Methods Insulin secretion from islets from Sprague-Dawley rats was measured in batch incubations. Cytoplasmic free Ca2+ concentration was measured from single beta-cells by fura-2-based microfluorometry. Results Triphenylphosphine oxide did not alter insulin secretion and [Ca2+](i) response triggered by KCl or fructose. It inhibited insulin secretion in response to glucose, l-arginine, and glucagon-like peptide 1. It also inhibited glucose-induced insulin secretion by mechanisms that are independent of the adenosine triphosphate-sensitive potassium channels and [Ca2+](i) increase. Conclusions Our results suggest that in the rat islets, TRPM5 is involved in mediating insulin secretion by glucose and l-arginine and in potentiating the glucose-induced insulin secretion by glucagon-like peptide 1.

  • 13.
    Kulke, Matthew H.
    et al.
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Hoersch, Dieter
    Zentralklin Bad Berka, Bad Berka, Germany..
    Caplin, Martyn
    Royal Free Hosp, Pond St, London NW3 2QG, England..
    Anthony, Lowell
    Univ Kentucky, Lexington, KY USA..
    Bergsland, Emily
    UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA..
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology. Uppsala Univ, Uppsala, Sweden..
    Warner, Richard
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA..
    Lombard-Bohas, Catherine
    Hos Civils Lyon, Hop Edouard Herriot, Lyon, France..
    Kunz, Pamela
    Stanford Univ, Palo Alto, CA 94304 USA..
    Grande, Enrique
    Hosp Univ Ramon & Cajal, Madrid, Spain..
    Valle, Juan W.
    Univ Manchester, Christie NHS Fdon Trust, Manchester, Lancs, England..
    Fleming, Douglas
    Ipsen BioSci, Cambridge, MA USA..
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Banks, Phillip
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Jackson, Shanna
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Wheeler, Darren
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Zambrowicz, Brian
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Sands, Arthur
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Pavel, Marianne
    Charite, D-13353 Berlin, Germany..
    Telotristat Etiprate Shows Benefit in Treating Patients With Carcinoid Syndrome That is Inadequately Controlled by Somatostatin Analog Therapy in the Phase 3 TELESTAR Clinical Trial2016In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 45, no 3, 478-478 p.Article in journal (Other academic)
  • 14. Larsson-Nyrén, Gerd
    et al.
    Grapengiesser, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Hellman, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Phospholipase A2 is important for glucose induction of rhythmic Ca2+ signals in pancreatic beta cells2007In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 35, no 2, 173-179 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Pancreatic beta cells respond to glucose stimulation with pulses of insulin release generated by oscillatory rises of the cytoplasmic Ca2+ concentration ([Ca2+]i). The observation that exposure to external ATP and other activators of cytoplasmic phospholipase A2 (cPLA2) rapidly induces rises of [Ca2+]i similar to ordinary oscillations made it important to analyze whether suppression of the cPLA2 activity affects glucose-induced [Ca2+]i rhythmicity in pancreatic beta cells. METHODS: Ratiometric fura-2 technique was used for measuring [Ca2+]i in single beta cells and small aggregates prepared from ob/ob mouse islets. RESULTS: Testing the effects of different inhibitors of cPLA2 in the presence of 20 mM glucose, it was found that N-(p-amylcinnamoyl)anthranilic acid (ACA) removed the oscillations at a concentration of 25 microM, arachidonyl trifluoromethyl ketone (AACOCF3) at 10 microM, and bromoenol lactone (BEL) at 10 to 15 microM. Withdrawal of ACA and BEL resulted in reappearance of the oscillations. Suppression of the arachidonic acid production by addition of 5 microM of the diacylglycerol lipase inhibitor 1,6-bis-(cyclohexyloximinocarbonylamino)-hexane (RHC 80267) effectively removed the [Ca2+]i oscillations, an effect reversed by removal of the inhibitor or addition of 100 microM tolbutamide. Suppression of the arachidonic acid production had a restrictive influence also on the transients of [Ca2+]i supposed to synchronize the beta-cell rhythmicity. Although less sensitive than the oscillations, most transients disappeared during exposure to 50 microM ACA or 35 microM RHC 80267. CONCLUSIONS: The results support the idea that cyclic variations of cPLA2 activity are important for the generation and synchronization of the beta-cell [Ca2+]i oscillations responsible for pulsatile release of insulin.

  • 15.
    Lejonklou, Margareta Halin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Edfeldt, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Johansson, Térèse A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Neurogenin 3 and neurogenic differentiation 1 are retained in the cytoplasm of multiple endocrine neoplasia type 1 islet and pancreatic endocrine tumor cells2009In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 38, no 3, 259-266 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    To investigate if transcription factors involved in pancreatic differentiation and regeneration are present in pancreatic endocrine tumors and if they are differentially expressed in normal pancreas compared with multiple endocrine neoplasia type 1 (MEN1) nontumorous pancreas.

    METHODS:

    The expression of neurogenin 3 (NEUROG3), neurogenic differentiation 1 (NEUROD1), POU class 3 homeobox 4 (POU3F4), pancreatic duodenal homeobox factor 1 (PDX1), ribosomal protein L10 (RPL10), delta-like 1 homolog (Drosophila; DLK1), and menin was analyzed by immunohistochemistry in normal pancreas and pancreatic endocrine tumors from 6 patients with MEN1 and 16 patients with sporadic tumors, as well as pancreatic specimens from Men1 heterozygous and wild type mice. Quantitative polymerase chain reaction was performed in a subset of human tumors.

    RESULTS:

    Tumors and MEN1 nontumorous endocrine cells showed a prominent cytoplasmatic NEUROG3 and NEUROD1 expression. These factors were significantly more expressed in the cytoplasm of Men1 heterozygous mouse islet cells compared with wild type islets; the latter showed an exclusively nuclear reactivity. The degree of Pou3f4, Rpl10, and Dlk1 immunoreactivities differed significantly between islets of heterozygous and wild type mice. The expressions of RPL10 and NEUROD1 were prominent in the MEN1 human and heterozygous mouse exocrine pancreas. Insulinomas had significantly higher PDX1 and DLK1 messenger RNA levels compared with other tumor types.

    CONCLUSIONS:

    Transcription factors involved in pancreatic development show altered expression and subcellular localization in MEN1 nontumorous pancreas and pancreatic endocrine tumors.

  • 16. Leung, Po Sing
    et al.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology, Diabetes and Metabolism.
    Pancreatic islet renin angiotensin system: its novel roles in islet function and in diabetes mellitus2005In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 30, no 4, 293-298 p.Article in journal (Refereed)
    Abstract [en]

    Several regulatory systems are implicated in the regulation of islet function and [beta] cell mass. Of great interest in this context are some endocrine, paracrine/autocrine, and intracrine regulators. These include, to name but a few, the gut peptides, growth factors, prostaglandins, and some vasoactive mediators such as nitric oxide, bradykinins, endothelins, and angiotensins. Apart from its potent vasoconstrictor actions, the renin-angiotensin system (RAS) that generates angiotensin II has several novel functions-stimulation and inhibition of cell proliferation; induction of apoptosis; generation of reactive oxygen species; regulation of hormone secretion; and proinflammatory and profibrogenic actions. In the pancreas, recent evidence supports the presence of an islet RAS, which is subject to activation by islet transplantation and diabetes. Such a local islet RAS, if activated, may drive islet fibrosis and reduce islet blood flow, oxygen tension, and insulin biosynthesis. Moreover, activation of an islet RAS may drive the synthesis of reactive oxygen species, cause oxidative stress-induced [beta] cell dysfunction and apoptosis, and thus contribute to the islet dysfunction seen in type 2 diabetes and after islet transplantation. Blockade of the RAS could contribute to the development of novel therapeutic strategies in the prevention and treatment of patients with diabetes and in islet transplantation.

  • 17.
    Li, Su-Chen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Martijn, Cecile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Essaghir, Ahmed
    Lloyd, Ricardo V.
    Demoulin, Jean-Baptiste
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Giandomenico, Valeria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    B12Global MicroRNA Profiling of Small Intestine Neuroendocrine Tumors (SI-NETs) and Establishment of a Method to Study Serum MicroRNA Expression From the Same Tumors2013In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, no 2, 377-377 p.Article in journal (Other academic)
  • 18.
    Marabita, Francesco
    et al.
    Soder Sjukhuset, Ctr Mol Med, Res Ctr, Karolinska Inst,Unit Computat Med, Stockholm, Sweden.;Soder Sjukhuset, Res Ctr, Karolinska Inst, Bioinformat Infrastruct Life Sci, Stockholm, Sweden.;Soder Sjukhuset, Res Ctr, Karolinska Inst, Dept Clin Sci & Educ, 3rd floor, SE-11883 Stockholm, Sweden..
    Islam, Md. Shahidul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Soder Sjukhuset, Res Ctr, Karolinska Inst, Dept Clin Sci & Educ, 3rd floor, SE-11883 Stockholm, Sweden..
    Expression of Transient Receptor Potential Channels in the Purified Human Pancreatic beta-Cells2017In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 1, 97-101 p.Article in journal (Refereed)
    Abstract [en]

    Objective: Members of the transient receptor potential (TRP) channels are involved in mediating the electrical excitability and stimulus-secretion coupling in the pancreatic beta-cells. The expression and the relative abundance of different TRP channels in the human beta-cells are unknown. The objective of this study was to examine the expression of the TRP channels and their relative abundance in the human beta-cell. Methods: RNA sequencing data obtained from human islets, fluorescence-activated cell sorting-purified human beta-cell and human pancreatic acinar cells were analyzed. Gene counts and fragments per kilobase per million mapped reads were obtained. Results: Among the TRPC family only the TRPC1 was expressed in the human beta-cell. TRPV1 channels were not expressed in the human beta-cells. Among the TRPM family, TRPM4, TRPM7, TRPM2, and TRPM3 were expressed in the human beta-cell. Of the remaining TRP channels, TRPP2, TRPML1, and TRPML3 were expressed in these cells. Conclusions: By analyzing the RNA sequencing data, we have detected for the first time the TRP channels that are expressed in the purified human beta-cells, in comparison to the other relevant pancreatic cell types. Our study provides an opportunity to focus on these TRP channels for a better understanding of the electrophysiology and stimulus-secretion coupling in these cells.

  • 19.
    Neoptolemos, J. P.
    et al.
    Univ Liverpool, Liverpool, Merseyside, England..
    Palmer, D.
    Univ Liverpool, Liverpool, Merseyside, England..
    Ghaneh, P.
    Univ Liverpool, Liverpool, Merseyside, England..
    Valle, J.
    Univ Manchester, Manchester, Lancs, England.;Christie, Manchester, Lancs, England..
    Cunningham, D.
    Royal Marsden Hosp, London, England..
    Wadsley, J.
    Weston Pk Hosp, Sheffield, S Yorkshire, England..
    Meyer, T.
    Royal Free Hosp, London, England..
    Anthoney, A.
    St James Univ Hosp, Leeds, W Yorkshire, England..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Falk, S.
    Bristol Haematol & Oncol Ctr, Bristol, Avon, England..
    Lind, P.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Izbicki, J.
    Univ Hamburg, Med Inst UKE, Hamburg, Germany..
    Middleton, G.
    Royal Surrey Cty Hosp, Guildford, Surrey, England..
    Ross, P.
    Guys Hosp, London, England..
    Wasan, H.
    Hammersmith Hosp, London, England..
    McDonald, A.
    Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland..
    Crosby, T.
    Velindre Hosp, Cardiff, S Glam, Wales..
    Psarelli, E.
    Univ Liverpool, Liverpool, Merseyside, England..
    Hammel, P.
    Hop Beaujon, Clichy, France..
    Buechler, M. W.
    Heidelberg Univ, Heidelberg, Germany..
    ESPAC-4: A Multicenter, International, Randomized Controlled Phase III Trial of Adjuvant Combination Chemotherapy of Gemcitabine (GEM) and Capecitabine (CAP), Versus Monotherapy Gemcitabine in Patients With Resected Pancreatic Ductal Adenocarcinoma2016In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 45, no 10, 1529-1529 p.Article in journal (Refereed)
  • 20.
    Ngamjariyawat, Anongnad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuroanatomy.
    Turpaev, Kyril
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Welsh, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Kozlova, Elena N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuroanatomy.
    Coculture of Insulin-Producing RIN5AH Cells With Neural Crest Stem Cells Protects Partially Against Cytokine-Induced Cell Death2012In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 41, no 3, 490-492 p.Article in journal (Refereed)
  • 21. Oberg-Welsh, C
    et al.
    Welsh, M
    Effects of certain growth factors on in vitro maturation of rat fetal islet-like structures.1996In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 12, no 4, 334-9 p.Article in journal (Refereed)
    Abstract [en]

    We have previously studied the expression of protein tyrosine kinases in different preparations of insulin producing cells by polymerase chain reaction (PCR). Among the tyrosine kinases thus identified were the fibroblast growth factor receptor-4 (FGFR-4), c-Kit, the insulin-like growth factor (IGF-I) receptor, and the cytoplasmic tyrosine kinase Jak2, which associates with the activated receptor for growth hormone (GH). To elucidate the putative biological effects of the receptors identified, fetal islet-like structures were cultured in the absence or presence of the ligands to the receptors identified, namely, acidic FGF (aFGF), stem-cell factor (SCF), IGF-I, and GH, whereafter insulin and DNA contents as well as insulin secretion to the culture medium were determined. Nerve growth factor (NGF), the ligand to the tyrosine kinase receptor Trk-A, was also included. aFGF and GH were found to stimulate insulin release to the culture medium, whereas SCF augmented insulin contents/DNA as well as islet DNA contents. No effects of NGF or IGF-I were detected. Immunohistochemical studies of fetal rat pancreas showed localization of the c-Kit protein to the pancreatic ducts, whereas immuno-reactivity against FGFR-4 could be detected in both endocrine and exocrine parts of the pancreas as well as in the pancreatic ducts. It is concluded that tyrosine kinase receptors may be involved in the maturation of pancreatic beta cells.

  • 22.
    Pavel, Marianne
    et al.
    Charite Univ Med Berlin, CVK, Med Klin Schwerpunkt, Berlin, Germany..
    Gross, David
    Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel..
    Benavent, Marta
    Hosp Univ Virgen Rocio, Seville, Spain..
    Caplin, Martyn
    Royal Free Hosp, Hampstead, England..
    Perros, Petros
    Royal Victoria Infirm, Newcastle Upon Tyne, Tyne & Wear, England..
    Srirajaskanthan, Raj
    Kings Coll Hosp London, London, England..
    Valle, Juan
    Christie NHS Fdn Trust, Manchester, Lancs, England..
    Warner, Richard
    Mt Sinai Sch Med, New York, NY USA..
    Kulke, Matthew
    Dana Farber Canc Inst, Boston, MA USA..
    Anthony, Lowell
    Univ Kentucky, Lexington, KY 40506 USA..
    Kunz, Pamela
    Stanford Univ, Stanford, CA 94305 USA..
    Hoersch, Dieter
    Klin Innere Med, Bad Berka, Germany..
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Lapuerta, Pablo
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Jackson, Shanna
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Banks, Phillip
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Biran, Talia
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Garcia-Carbonero, Rocio
    Hosp Univ Doce Octubre, Madrid, Spain..
    Efficacy and Safety Results of Telotristat Ethyl in Patients With Carcinoid Syndrome During the Double-blind Treatment Period of the TELECAST Phase 3 Clinical Trial2017In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 3, 434-435 p.Article in journal (Other academic)
  • 23. Phan, Alexandria T
    et al.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Choi, Junsung
    Harrison, Lynn H
    Hassan, Manal M
    Strosberg, Jonathan R
    Krenning, Eric P
    Kocha, Walter
    Woltering, Eugene A
    Maples, William J
    NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the thorax (includes lung and thymus)2010In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 39, no 6, 784-798 p.Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) of the thorax, including bronchial and thymic neuroendocrine NETs, are often referred to as NETs of the foregut. The incidence and prevalence of NETs are increasing in the United States as demonstrated in the Surveillance, Epidemiology, and End Results from 1973 to 2004 (J Clin Oncol. 2008;26[18]:3063-3072). Although the majority of bronchial and thymic NETs are sporadic, approximately 5% to 10% can be associated with hereditary syndrome, multiple endocrine neoplasms type 1 (Nat Rev Cancer. 2005;5[5]:367-375). Diagnosis is made by tissue pathology, allowing for characterization and classification of the NET. Radiologic evaluation is performed to determine the extent of disease involvement. Clinical symptoms from hormonal overproduction or from paraneoplastic processes are medically managed to improve patients' quality of life. Locoregional disease can be curative with surgery; however, distant or metastatic disease is rarely curable. Therapeutic options for metastatic/advanced NETs of the thorax are mainly to palliate symptoms. Final treatment recommendations for patients with either bronchial or thymic NETs should be individualized, weighing the risks and benefits of therapy.

  • 24. Portela-Gomes, Guida M.
    et al.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Westermark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Somatostatin Receptor Subtypes in Human Type 2 Diabetic Islets2010In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 39, no 6, 836-842 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES

    Somatostatin inhibits hormone release through 5 G protein-coupled somatostatin receptors (sst1-sst5). However, the role of somatostatin in islet physiology is not fully known. The immunoreactivity to sst1 to sst5 in normal human endocrine pancreas has been described. The present study reports the expression of sst1 to sst5 in human pancreatic islets with type 2 diabetes mellitus.

    METHODS

    Pancreatic autopsy specimens from individuals with type 2 diabetes mellitus and matched controls were double immunostained to demonstrate sst1 to sst5 in the major islet cell types.

    RESULTS

    Most apparent differences in type 2 diabetic islets were the lack of sst1 and sst4 in glucagon cells and sst1-3 and 4 in somatostatin cells, whereas minor changes were demonstrated in insulin cells. The pancreatic polypeptide cells showed a reversed staining pattern in diabetic islets compared with the controls.

    CONCLUSIONS

    In type 2 diabetes mellitus, the sst pattern differed from that of the controls in somatostatin, pancreatic polypeptide, and glucagon cells, to a minor extent in insulin cells. It is unclear whether the changes in sst patterns are primarily due to the diabetes or secondary to metabolic disturbances. However, this study may be the basis for further functional studies to evaluate the role of sst1 to sst5 in the diabetic state.

  • 25.
    Sandberg, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Johansson, Sophie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Q Med AB, Uppsala, Sweden..
    Sagulin, Lisbeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Johansson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Scavenging Endothelium of Pancreatic Islets Differential Expression of Stabilin-1 and Stabilin-2 in Mice and Humans2017In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 1, E4-E5 p.Article in journal (Other academic)
  • 26. Sorbye, Halfdan
    et al.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Langer, Seppo
    Vestermark, Lena
    Holt, Nanna
    Osterlund, Pia
    Dueland, Svein
    Hofsli, Eva
    Guren, Marianne
    Ohrling, Katarina
    Birkemeyer, Elke
    Thiis-Evensen, Espen
    Biagini, Matteo
    Gronbaek, Henning
    Soveri, Leena-Maija
    Olsen, Ingrid Holst
    Federspiel, Birgitte
    Assmus, Jurg
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Knigge, Ulrich
    Ki-67 Proliferative Index Predicts Response to Chemotherapy and Survival in 252 Patients with High-Grade Gastrointestinal Neuroendocrine Carcinoma (WHO G3)2013In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 42, no 2, 382-382 p.Article in journal (Other academic)
  • 27.
    Staaf, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Labmayr, Viktor
    Paulmichl, Katharina
    Manell, Hannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cen, Jing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ciba, Iris
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Dahlbom, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Roomp, Kirsten
    Anderwald, Christian-Heinz
    Meissnitzer, Matthias
    Schneider, Reinhard
    Forslund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Widhalm, Kurt
    Bergquist, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergsten, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Weghuber, Daniel
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Pancreatic Fat Is Associated With Metabolic Syndrome and Visceral Fat but Not Beta-Cell Function or Body Mass Index in Pediatric Obesity2017In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 46, no 3, 358-365 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Adolescents with obesity have increased risk of type 2 diabetes and metabolic syndrome (MetS). Pancreatic fat has been related to these conditions; however, little is known about associations in pediatric obesity. The present study was designed to explore these associations further.

    METHODS: We examined 116 subjects, 90 with obesity. Anthropometry, MetS, blood samples, and oral glucose tolerance tests were assessed using standard techniques. Pancreatic fat fraction (PFF) and other fat depots were quantified using magnetic resonance imaging.

    RESULTS: The PFF was elevated in subjects with obesity. No association between PFF and body mass index-standard deviation score (BMI-SDS) was found in the obesity subcohort. Pancreatic fat fraction correlated to Insulin Secretion Sensitivity Index-2 and Homeostatic Model Assessment of Insulin Resistance in simple regression; however, when using adjusted regression and correcting for BMI-SDS and other fat compartments, PFF correlated only to visceral adipose tissue and fasting glucose. Highest levels of PFF were found in subjects with obesity and MetS.

    CONCLUSIONS: In adolescents with obesity, PFF is elevated and associatedto MetS, fasting glucose, and visceral adipose tissue but not to beta-cellfunction, glucose tolerance, or BMI-SDS. This study demonstrates thatconclusions regarding PFF and its associations depend on the body massfeatures of the cohort.

  • 28. Strosberg, Jonathan R.
    et al.
    Yao, James C.
    Bajetta, Emilio
    Aout, Mounir
    Bakker, Bert
    Hainsworth, John D.
    Ruszniewski, Philippe B.
    Van Cutsem, Eric
    Öberg, Kjell E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pavel, Marianne E.
    Efficacy of Octreotide Long-Acting Repeatable (OCT) From the Phase III RADIANT-2 Study in Patients With Advanced Neuroendocrine Tumors (NET): A Post-Hoc Analysis of the Placebo (PBO) Arm With Updated Survival Data2015In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 44, no 2, 359-359 p.Article in journal (Other academic)
  • 29.
    Strosberg, Jonathan
    et al.
    Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA..
    Wolin, Edward
    Univ Kentucky, Markey Canc Ctr, Lexington, KY USA..
    Chasen, Beth
    Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA..
    Kulke, Matthew
    Dana Farber Canc Inst, Boston, MA 02115 USA..
    Bushnell, David
    Univ Iowa, Iowa City, IA USA..
    Caplin, Martyn
    Royal Free Hosp, Pond St, London NW3 2QG, England..
    Baum, Richard P.
    Zentralklin, Bad Berka, Germany..
    Mittra, Erik
    Stanford Univ, Med Ctr, Stanford, CA 94305 USA..
    Hobday, Timothy
    Mayo Clin, Coll Med, Rochester, MN USA..
    Hendifar, Andrew
    Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA..
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Sierra, Maribel Lopera
    Adv Accelerator Applicat, New York, NY USA..
    Kwekkeboom, Dik
    Erasmus MC, Rotterdam, Netherlands..
    Ruszniewski, Philippe
    Hop Beaujon, Clichy, France..
    Krenning, Eric
    Erasmus MC, Rotterdam, Netherlands..
    177-Lu-Dotatate Significantly Improves Progression-Free Survival in Patients with Midgut Neuroendocrine Tumors: Results of the Phase III NETTER-1 Trial2016In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 45, no 3, 483-483 p.Article in journal (Other academic)
  • 30. Wolin, Edward M.
    et al.
    Jarzab, Barbara
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Walter, Thomas
    Toumpanakis, Christos
    Morse, Michael
    Tomassetti, Paola
    Weber, Matthias
    Fogelman, David
    Ramage, John
    Poon, Donald
    Huang, Jerry
    Hudson, Michelle
    Li, Jiang
    Pasieka, Janice L.
    Mahamat, Abakar
    Swahn, Fredrik
    Newell-Price, John
    Mansoor, Was
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    A Multicenter, Randomized, Blinded, Phase 3 Study of Pasireotide LAR vs Octreotide LAR in Patients with Metastatic Neuroendocrine Tumors (NET) with Disease-Related Symptoms Inadequately Controlled by Somatostatin Analogs2014In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 43, no 3, 508-508 p.Article in journal (Other academic)
  • 31.
    Wroblewski, R
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Pålsgård, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Juntti-Berggren, L
    Berggren, P-O
    Roomans, G M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    X-ray microanalysis of in situ and isolated pancreatic islets1998In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 16, no 2, 134-140 p.Article in journal (Refereed)
    Abstract [en]

    The effect of stimulation of insulin secretion in pancreatic beta cells on the elemental composition ofthese cells was investigated by x-ray microanalysis. In vitro experiments on isolated islets ofLangerhans from ob/ob mice were compared to in situ experiments. The only significant difference inthe elemental composition of beta cells from ob/ob mice versus their lean counterparts is a lower Ca concentration in the ob/ob animals. The nucleus of the beta cells has a higher concentration of P, K, and Na than the cytoplasm, which has a higher concentration of S and Cl. No polarized ion distributionin the cytoplasm of the beta cells was observed. Isolated beta cells show a higher concentration of Na and Cl and a lower concentration of K than their in situ counterparts. Stimulation of insulin secretion with glucose both in situ and in vitro showed only very small effects on the elemental composition of the beta cells: a tendency to a decreased P content was noted. In vitro experiments using stimulation with high extracellular K+ showed, in addition, a small increase in the intracellular K concentration. Inconclusion, while the elemental content of beta cells in vitro differs from that in situ, the response to glucose stimulation appears to be similar in both systems.

  • 32. Yao, James C.
    et al.
    Öberg, Kjell E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hainsworth, John D.
    Lam, Du
    Stergiopolos, Sotirios G.
    Rouyrre, Nicolas
    Peeters, Marc
    Baudin, Eric
    Gross, David
    Pavel, Marianne E.
    Everolimus Plus Octreotide Long-Acting Repeatable (LAR) for the Treatment of Advanced Neuroendocrine Tumors (NET) Associated with Carcinoid Syndrome: Updated Overall Survival Results from RADIANT-2 Study2014In: Pancreas, ISSN 0885-3177, E-ISSN 1536-4828, Vol. 43, no 3, 508-509 p.Article in journal (Other academic)
1 - 32 of 32
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