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https://www.readbyqxmd.com/read/28449948/sunitinib-specifically-augments-glucose-induced-insulin-secretion
#1
Stefan Z Lutz, Axel Ullrich, Hans-Ulrich Häring, Susanne Ullrich, Felicia Gerst
The tyrosine kinase inhibitor sunitinib is used for the treatment of numerous cancers in humans. In diabetic patients, sunitinib lowers blood glucose levels and improves glycaemic control. This study aims to analyse whether sunitinib has specific and direct effects on insulin secreting β-cells. Regulation of insulin secretion, of cellular cAMP levels and activation of signalling pathways were examined upon exposure of rat insulinoma INS-1E cells to sunitinib under specific stimulatory and inhibitory conditions...
April 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28445528/baicalein-protects-rat-insulinoma-ins-1-cells-from-palmitate-induced-lipotoxicity-by-inducing-ho-1
#2
Hyun Jeong Kwak, Dongki Yang, Yongha Hwang, Hee-Sook Jun, Hyae Gyeong Cheon
OBJECTIVE: β-Cell dysfunction plays a central role in the pathogenesis of type 2 diabetes (T2D), and the identification of novel approaches to improve β-cell function is essential to treat this disease. Baicalein, a flavonoid originally isolated from the root of Scutellaria Baicalensis, has been shown to have beneficial effects on β-cell function. Here, the authors investigated the molecular mechanism responsible for the protective effects of baicalein against palmitate (PA)-induced impaired β-cell function, and placed focus on the role of heme oxygenase (HO)-1...
2017: PloS One
https://www.readbyqxmd.com/read/28432716/deciphering-tacrolimus-induced-toxicity-in-pancreatic-%C3%AE-cells
#3
J Triñanes, A E Rodriguez-Rodriguez, Y Brito, A Wagner, A P J De Vries, G Cuesto, A Acebes, E Salido, A Torres, E Porrini
β-cell transcription factors like: FoxO1, MafA, PDX-1, NeuroD, are dysfunctional in type 2 diabetes (T2DM). PTDM resembles T2DM and reflects interaction between pre-transplant insulin resistance and immunosuppressants, mainly calcineurin inhibitors. We evaluated the effect of tacrolimus, cyclosporine-A and metabolic stressors (glucose+palmitate) on insulinoma β-cells (INS-1) in vitro and in pancreata of obese and lean Zucker rats. Cells were cultured for five days with 100μM palmitate and 22mM glucose; cyclosporin-A (250ng/mL) or tacrolimus (15ng/mL) were added the last 48h...
April 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28428639/obestatin-stimulates-glucose-induced-insulin-secretion-through-ghrelin-receptor-ghs-r
#4
Geetali Pradhan, Chia-Shan Wu, Jong Han Lee, Preeti Kanikarla, Shaodong Guo, Vijay K Yechoor, Susan L Samson, Yuxiang Sun
Orexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin's effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R), but the physiologically relevant receptor of obestatin remains debatable. Here we have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo, and tested whether obestatin regulates insulin secretion through GHS-R...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427440/hypoglycemia-identified-by-a-continuous-glucose-monitoring-system-in-a-second-trimester-pregnant-woman-with-insulinoma-a-case-report
#5
Marjeta Tomazic, Andrej Janez, Maja Ravnik Oblak
BACKGROUND: Insulinoma associated with pregnancy is a very rare condition and can be difficult to diagnose. Here, we present an interesting case of insulinoma occurring during pregnancy with special attention paid to the use of a continuous glucose monitoring system to detect hypoglycemia. CASE PRESENTATION: A 36-year-old white woman in the second trimester of pregnancy presented with recurrent episodes of hypoglycemia associated with neuroglycopenic symptoms. The use of a continuous glucose monitoring system confirmed hypoglycemia...
April 21, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28422824/pancreatic-carcinoids-serotonin-producing-pancreatic-neuroendocrine-neoplasms-report-of-5-cases-and-review-of-the-literature
#6
Nikolaos Tsoukalas, Eleftherios Chatzellis, Dimitra Rontogianni, Krystallenia I Alexandraki, Georgios Boutzios, Anna Angelousi, Gregory Kaltsas
INTRODUCTION: Pancreatic neuroendocrine neoplasms (pNENs) are relatively rare tumors representing 1% to 2% of all pancreatic neoplasms. These tumors can secrete a variety of biologically active substances giving rise to distinct clinical symptoms or can be clinically nonfunctioning. Apart from insulinomas and gastrinomas, which constitute the majority of functioning pNENs, some tumors may secrete serotonin presenting with the features of the carcinoid syndrome. These so-called pancreatic carcinoids are considered relatively rare tumors and are associated with increased urinary levels of 5-hydroxyindoleacetic acid (5-HIAA)...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28419614/prospective-comparison-of-biphasic-contrast-enhanced-ct-volume-perfusion-ct-and-3-tesla-mri-with-diffusion-weighted-imaging-for-insulinoma-detection
#7
Liang Zhu, Huadan Xue, Zhaoyong Sun, Ping Li, Tianyi Qian, Xiaoping Xing, Naishi Li, Yupei Zhao, Wenming Wu, Zhengyu Jin
PURPOSE: To evaluate the diagnostic performance of biphasic contrast-enhanced CT (CECT), volume perfusion CT (VPCT) and 3 Tesla MRI with diffusion-weighted imaging (DWI), in patients with clinically suspected insulinomas. MATERIALS AND METHODS: This prospective study was approved by the institutional review board. Sixty-four patients with clinically suspected insulinomas underwent biphasic CECT, VPCT, and 3T MR with DWI. Two radiologists independently determined the presence/absence of tumor using a 5-scale confidence level...
April 17, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28409826/glycogen-phosphorylase-inhibition-improves-%C3%AE-cell-function
#8
Lilla Nagy, Judit Márton, András Vida, Gréta Kis, Éva Bokor, Sándor Kun, Mónika Gönczi, Tibor Docsa, Attila Tóth, Miklós Antal, Pál Gergely, Balázs Csóka, Pal Pacher, László Somsák, Péter Bai
BACKGROUND AND PURPOSE: Glycogen phosphorylase (GP) is the key enzyme for glycogen degradation. GP inhibitors (GPi-s) are glucose lowering agents trapping glucose in the liver as glycogen. Glycogen metabolism has implications in β-cell function; glycogen degradation can maintain cellular glucose levels, which feeds into catabolism to maintain insulin secretion, and elevated glycogen degradation levels contribute to glucotoxicity. The purpose of this study was to assess whether influencing glycogen metabolism in β-cells by GPi-s impacts β-cell function...
April 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28409274/toward-molecular-imaging-of-the-free-fatty-acid-receptor-1
#9
Ewa Hellström-Lindahl, Ola Åberg, Cecilia Ericsson, Gavin O'Mahony, Peter Johnström, Stanko Skrtic, Olof Eriksson
AIMS: Molecular imaging of the free fatty acid receptor 1 (FFAR1) would be a valuable tool for drug development by enabling in vivo target engagement studies in human. It has also been suggested as a putative target for beta cell imaging, but the inherent lipophilicity of most FFAR1 binders produces high off-target binding, which has hampered progress in this area. The aim of this study was to generate a suitable lead compound for further PET labeling. METHODS: In order to identify a lead compound for future PET labeling for quantitative imaging of FFAR1 in human, we evaluated tritiated small molecule FFAR1 binding probes ([(3)H]AZ1, [(3)H]AZ2 and [(3)H]TAK-875) for their off-target binding, receptor density and affinity in human pancreatic tissue (islets and exocrine) and rodent insulinoma...
April 13, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28400403/molecular-imaging-in-the-investigation-of-hypoglycaemic-syndromes-and-their-management
#10
David A Pattison, Rodney J Hicks
There has been recent progress in molecular imaging using a variety of cellular targets for the investigation of adult non-diabetic hypoglycaemic syndromes and its integration into patient management. These targets include peptide receptors - somatostatin receptors (SSTR) and glucagon-like peptide-1 receptor (GLP-1R) - the Amine Precursor Uptake and Decarboxylation system utilising the diphydroxyphenylaline (DOPA) analogue 6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine (18F-FDOPA), and glycolytic metabolism with 2-[18F]Fluoro-2-Deoxy-D-Glucose (FDG)...
April 11, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28388722/thyroid-and-islet-autoantibodies-predict-autoimmune-thyroid-disease-at-type-1-diabetes-diagnosis
#11
Berglind Jonsdottir, Christer Larsson, Annelie Carlsson, Gun Forsander, Sten Anders Ivarsson, Åke Lernmark, Johnny Ludvigsson, Claude Marcus, Ulf Samuelsson, Eva Örtqvist, Helena Elding Larsson
Context: Screening of autoimmune thyroid disease in children with type 1 diabetes is important but varies between clinics. Objective: To determine the predictive value of thyroid autoantibodies, thyroid function, islet autoantibodies, and HLA-DQ at diagnosis of type 1 diabetes for autoimmune thyroid disease during follow-up. Setting: Forty-three Swedish pediatric endocrinology units. Design, Patients, and Main Outcome Measures: At diagnosis of type 1 diabetes, autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase (GADA), insulin, insulinoma-associated protein-2, and 3 variants of zinc transporter 8 (ZnT8W/R/QA) HLA-DQA1-B1 genotypes and thyroid function were analyzed in 2433 children...
April 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28383837/-clinical-approach-of-a-suspicion-of-hypoglycaemic-malaise-in-a-nondiabetic-adult
#12
A J Scheen, N Paquot, P J Lefèbvre
Malaises are often attributed to hypoglycaemia in nondiabetic people who don't have any other serious medical problem. However, such a diagnosis is often overused, because not really demonstrated in most instances. The diagnosis of hypoglycaemia should be structured, based upon the Whipple triad. First, the anamnesis must search for adrenergic and neuroglucopenic symptoms that suggest hypoglycaemia. Afterwards, hypoglycaemia must be authentified by a measurement of a low glucose level at the time of a malaise...
September 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28381450/management-of-endocrine-disease-pathogenesis-and-management-of-hypoglycemia
#13
Nana Esi Kittah, Adrian Vella
Glucose is the main substrate utilized by the brain and as such multiple regulatory mechanisms exist to maintain glucose concentrations. When these mechanisms fail or are defective hypoglycemia ensues. Due to these robust mechanisms hypoglycemia is uncommon and usually occurs in the setting of the treatment of diabetes using glucose- lowering agents such as sulfonylureas or insulin. The symptoms of hypoglycemia are non-specific and as such it is important to confirm hypoglycemia by establishing the presence of Whipple's triad prior to embarking on an evaluation for hypoglycemia...
April 5, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28376584/a-novel-multi-epitope-vaccine-based-on-dipeptidyl-peptidase-4-prevents-streptozotocin-induced-diabetes-by-producing-anti-dpp4-antibody-and-immunomodulatory-effect-in-c57bl-6j-mice
#14
Zhixin Li, Jinzhi Fang, Rui Jiao, Xiaomin Wei, Yanjie Ma, Xiaoran Liu, Peng Cheng, Taiming Li
Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective destruction of insulin-producing β-cells leads to impaired glucose metabolism and its attendant complications. A series of Dipeptidyl peptidase 4 (DPP4) inhibitors have been developed and granted approval in the treatment of type 2 diabetes mellitus by inhibiting the enzymatic degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). An increasing number of studies have shown the potential benefits of DPP4 inhibitors for type 1 diabetes...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28374260/is-there-a-role-for-near-infrared-technology-in-laparoscopic-resection-of-pancreatic-neuroendocrine-tumors-results-of-the-colpan-colour-and-resect-the-pancreas-study
#15
Salvatore Paiella, Matteo De Pastena, Luca Landoni, Alessandro Esposito, Luca Casetti, Marco Miotto, Marco Ramera, Roberto Salvia, Erica Secchettin, Deborah Bonamini, Gessica Manzini, Mirko D'Onofrio, Giovanni Marchegiani, Claudio Bassi
BACKGROUND: The intraoperative identification of pancreatic neuroendocrine tumors (PanNETs) is of utmost importance to drive their laparoscopic resection. Near-infrared (NIR) surgery has emerged as a new technique for localizing tumors or neoplastic tissue. This study aimed to explore the results of the application of NIR in the laparoscopic resection of PanNETs. METHODS: Per protocol we enrolled ten subjects undergoing laparoscopic pancreatic surgery for PanNET from March 2016 to October 2016...
April 3, 2017: Surgical Endoscopy
https://www.readbyqxmd.com/read/28365524/pancreas-and-liver-uptake-of-new-radiolabeled-incretins-glp-1-and-exendin-4-in-models-of-diet-induced-and-diet-restricted-obesity
#16
Daniele Seo, Bluma Linkowski Faintuch, Erica Aparecida de Oliveira, Joel Faintuch
INTRODUCTION: Radiolabeled GLP-1 and its analog Exendin-4, have been employed in diabetes and insulinoma. No protocol in conventional Diet-Induced Obesity (DIO), and Diet-Restricted Obesity (DRO), has been identified. Aiming to assess pancreatic beta cell uptake in DIO and DRO, a protocol was designed. METHODS: GLP-1-βAla-HYNIC and HYNIC-βAla-Exendin-4 were labeled with technetium-99m. Four Swiss mouse models were adopted: Controls (C), Alloxan Diabetes Controls (ADC), DIO and DRO...
March 18, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28363490/geniposide-improves-insulin-production-and-reduces-apoptosis-in-high-glucose-induced-glucotoxic-insulinoma-cells
#17
L X Guo, J H Liu, X X Zheng, Z Y Yin, J Kosaraju, K Y Tam
Our previous work revealed that in the pancreatic β cell line, geniposide modulated ATP production and glucose-stimulated insulin secretion (GSIS) induced by the acute stimulation of high glucose concentration. However, the effects of geniposide on functional impairment and the mass of β-cells exposed to elevated levels of glucose remains unknown. In the present study, impaired GSIS and restrained proliferation were observed in the prolonged culture of insulinoma INS-1 cells with 33mM of glucose (high glucose)...
March 28, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28361831/evolving-management-of-insulinoma-experience-at-a-tertiary-care-centre
#18
Viveka P Jyotsna, Sujoy Pal, D Kandasamy, S Gamanagatti, P K Garg, N Raizada, Peush Sahni, C S Bal, N Tandon, A C Ammini
BACKGROUND & OBJECTIVES: Since our previous study in 2006, several new modalities for localization of cause of endogenous hyperinsulinemic hypoglycaemia such as multiphasic computed tomography (CT), multiphasic magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), intraoperative ultrasound, and intra-arterial calcium infusion with arterial stimulation venous sampling (ASVS) have become available. Therefore, to evaluate the relative usefulness of various imaging modalities to guide future management in terms of diagnosis and patient care, we analyzed presentation and management of patients of endogenous hyperinsulinemic hypoglycaemia...
November 2016: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28358174/minerva-chirurgica-2017-mar-27
#19
Eugenia Yiannakopoulou
Minimally invasive surgery has an established role in the treatment of patients with pNETs. Enucleation is an established treatment option for insulinomas. The necessity of organ sparing surgery is well established in the case of multiple pNETs. A number of studies have demonstrated the efficacy and safety of laparoscopic surgery for the treatment of pNETs. However, pNETs are rare, and large studies focusing on pNET patients are difficult to be designed unless multicentre experience is collected. Authors investigating the role of minimally invasive pancreatic surgery should be encouraged to report separately the results that involve patients presenting with pNETs...
March 27, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28358037/type-1-diabetes-mellitus
#20
REVIEW
Anastasia Katsarou, Soffia Gudbjörnsdottir, Araz Rawshani, Dana Dabelea, Ezio Bonifacio, Barbara J Anderson, Laura M Jacobsen, Desmond A Schatz, Åke Lernmark
Type 1 diabetes mellitus (T1DM), also known as autoimmune diabetes, is a chronic disease characterized by insulin deficiency due to pancreatic β-cell loss and leads to hyperglycaemia. Although the age of symptomatic onset is usually during childhood or adolescence, symptoms can sometimes develop much later. Although the aetiology of T1DM is not completely understood, the pathogenesis of the disease is thought to involve T cell-mediated destruction of β-cells. Islet-targeting autoantibodies that target insulin, 65 kDa glutamic acid decarboxylase, insulinoma-associated protein 2 and zinc transporter 8 - all of which are proteins associated with secretory granules in β-cells - are biomarkers of T1DM-associated autoimmunity that are found months to years before symptom onset, and can be used to identify and study individuals who are at risk of developing T1DM...
March 30, 2017: Nature Reviews. Disease Primers
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