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Insulinoma

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https://www.readbyqxmd.com/read/28539593/identification-of-the-matricellular-protein-fibulin-5-as-a-target-molecule-of-glucokinase-mediated-calcineurin-nfat-signaling-in-pancreatic-islets
#1
Tomoko Okuyama, Jun Shirakawa, Hiromi Yanagisawa, Mayu Kyohara, Shunsuke Yamazaki, Kazuki Tajima, Yu Togashi, Yasuo Terauchi
Glucokinase-mediated glucose signaling induces insulin secretion, proliferation, and apoptosis in pancreatic β-cells. However, the precise molecular mechanisms underlying these processes are not clearly understood. Here, we demonstrated that glucokinase activation using a glucokinase activator (GKA) significantly upregulated the expression of Fibulin-5 (Fbln5), a matricellular protein involved in matrix-cell signaling, in isolated mouse islets. The islet Fbln5 expression was induced by ambient glucose in a time- and dose-dependent manner and further enhanced by high-fat diet or the deletion of insulin receptor substrate 2 (IRS-2), whereas the GKA-induced increase in Fbln5 expression was diminished in Irs-2-deficient islets...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28536844/evaluation-of-neurotensin-receptor-1-as-a-potential-imaging-target-in-pancreatic-ductal-adenocarcinoma
#2
Xiaoqin Yin, Mengzhe Wang, Hui Wang, Huaifu Deng, Tingting He, Yue Tan, Zehua Zhu, Zhanhong Wu, Shuo Hu, Zibo Li
Pancreatic cancer is one of the deadliest human malignancies and lack of effective diagnostic and therapeutic methods. Accumulating evidence suggests that the neurotensin (NT) and neurotensin receptors (NTRs) play key roles in pancreatic adenocarcinoma growth and survival. In this study, we not only evaluate the NTR1 expression in pancreatic cancer patient samples, but also explore the PET and fluorescence imaging of NTR1 expression in pancreatic cancer animal models. The NTR1 expression was evaluated by immunohistochemistry staining in clinical patient tissue samples with pancreatic ductal adenocarcinoma, insulinoma, and pancreatitis...
May 23, 2017: Amino Acids
https://www.readbyqxmd.com/read/28534945/trb3-mediates-advanced-glycation-end-product-induced-apoptosis-of-pancreatic-%C3%AE-cells-through-the-protein-kinase-c-%C3%AE-pathway
#3
Meng Wang, Wenjian Zhang, Shiqing Xu, Liang Peng, Zai Wang, Honglin Liu, Qing Fang, Tingting Deng, Xiuli Men, Jinning Lou
Advanced glycation end products (AGEs), which accumulate in the body during the development of diabetes, may be one of the factors leading to pancreatic β-cell failure and reduced β-cell mass. However, the mechanisms responsible for AGE‑induced apoptosis remain unclear. This study identified the role and mechanisms of action of tribbles homolog 3 (TRB3) in AGE-induced β-cell oxidative damage and apoptosis. Rat insulinoma cells (INS-1) were treated with 200 µg/ml AGEs for 48 h, and cell apoptosis was then detected by TUNEL staining and flow cytometry...
May 16, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28527697/antibiotics-induce-mitonuclear-protein-imbalance-but-fail-to-inhibit-respiration-and-nutrient-activation-in-pancreatic-%C3%AE-cells
#4
Jaime Santo-Domingo, Isabelle Chareyron, Charlotte Broenimann, Steve Lassueur, Andreas Wiederkehr
Chloramphenicol and several other antibiotics targeting bacterial ribosomes inhibit mitochondrial protein translation. Inhibition of mitochondrial protein synthesis leads to mitonuclear protein imbalance and reduced respiratory rates as confirmed here in HeLa and PC12 cells. Unexpectedly, respiration in INS-1E insulinoma cells and primary human islets was unaltered in the presence of chloramphenicol. Resting respiratory rates and glucose stimulated acceleration of respiration were also not lowered when a range of antibiotics including, thiamphenicol, streptomycin, gentamycin and doxycycline known to interfere with bacterial protein synthesis were tested...
May 17, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28526880/prognostic-relevance-of-uch-l1-and-%C3%AE-internexin-in-pancreatic-neuroendocrine-tumors
#5
Yu-Li Song, Run Yu, Xin-Wei Qiao, Chun-Mei Bai, Chong-Mei Lu, Yu Xiao, Ding-Rong Zhong, Jie Chen, Yu-Pei Zhao, Tai-Ping Zhang, Tian-Tian Song, He-Li Gao, Ying-Hua Wan, Lin Shen, Jie Chen, Bin Lv, Jian-Jiang Hao, Ye Zhang, Laura Tang, Yuan-Jia Chen
Prognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28512677/heterogeneity-of-proliferative-markers-in-pancreatic-%C3%AE-cells-of-patients-with-severe-hypoglycemia-following-roux-en-y-gastric-bypass
#6
Mary-Elizabeth Patti, Allison B Goldfine, Jiang Hu, Dag Hoem, Anders Molven, Jeffrey Goldsmith, Wayne H Schwesinger, Stefano La Rosa, Franco Folli, Rohit N Kulkarni
AIMS: Severe postprandial hypoglycemia with neuroglycopenia is an increasingly recognized, debilitating complication of Roux-en-Y gastric bypass (RYGB) surgery. Increased secretion of insulin and incretin hormones is implicated in its pathogenesis. Histopathologic examination of pancreas has demonstrated increased islet size and/or nuclear diameter in post-RYGB patients who underwent pancreatectomy for severe refractory hypoglycemia with neuroglycopenia (RYGB + NG). We aimed to determine whether β-cell proliferation or apoptosis is altered in RYGB + NG...
May 17, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28512591/sporadic-insulinoma-as-a-rare-cause-of-recurrent-hypoglycemia-in-children
#7
Hedyeh Saneifard, Ahmad Khaleghnejad Tabari, Maryam Kazemi Aghdam, Mohadese Musavi Khorshidi, Ali Sheikhy
Insulinoma is a rare pancreatic tumor in children and adolescents. As a result of insulin hypersecretion, signs and symptoms are more commonly consequences of the pathophysiologic responses to hypoglycemia. According to rarity of this tumor in children and nonspecificity of clinical presentations, diagnosis of insulinoma in this group of patients is usually delayed. Early diagnosis is very important for preventing neurologic damage. In this case report, we present the case of a 10-year-old boy with signs and symptoms of hypoglycemia and final diagnosis of insulinoma...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28510792/a-systematic-review-of-proinsulin-secreting-pancreatic-neuroendocrine-tumors
#8
Timothy D Murtha, Beatrice C Lupsa, Sachin Majumdar, Dhanpat Jain, Ronald R Salem
BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous group of islet cell-derived neoplasms with a propensity toward hormone production. Among PNETs, proinsulin-secreting tumors (proinsulinomas) are exceedingly rare. The objective of this study is to collect and summarize the existing literature to provide a comprehensive evaluation of this uncommon disease. METHODS: A systematic review was performed to characterize the clinicopathologic features of proinsulinoma...
May 16, 2017: Journal of Gastrointestinal Surgery: Official Journal of the Society for Surgery of the Alimentary Tract
https://www.readbyqxmd.com/read/28510423/phycocyanin-functionalized-selenium-nanoparticles-reverse-palmitic-acid-induced-pancreatic-beta-cells-apoptosis-by-enhancing-cellular-uptake-and-blocking-ros-mediated-mitochondria-dysfunction
#9
Chang Liu, Yuanting Fu, Chang-E Li, Tianfeng Chen, Xiaoling Li
Accumulation of palmitic acid (PA) in human bodies could cause damage to pancreatic beta cells and lead to chronic diseases by generation of reactive oxygen species (ROS). Therefore, it is of great significance to search for nutrition available agents with antioxidant activity to protect pancreatic islet cells against PA-induced damage. Phycocyanin (PC) and selenium (Se) have been reported to have excellent antioxidant activity. In this study, PC-functionalized selenium nanoparticles (PC-SeNPs) were synthesized to investigate the in vitro protective effects on INS-1E rat insulinoma beta cells against PA-induced cell death...
May 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28507564/management-of-the-hormonal-syndrome-of-neuroendocrine-tumors
#10
Paweł Gut, Joanna Waligórska-Stachura, Agata Czarnywojtek, Nadia Sawicka-Gutaj, Maciej Bączyk, Katarzyna Ziemnicka, Jakub Fischbach, Kosma Woliński, Jarosław Kaznowski, Elżbieta Wrotkowska, Marek Ruchała
Gastroenteropancreatic neuroendocrine tumors (GEP/NET) are unusual and rare neoplasms that present many clinical challenges. They characteristically synthesize store and secrete a variety of peptides and neuroamines which can lead to the development of distinct clinical syndrome, however many are clinically silent until late presentation with mass effects. Management strategies include surgery cure and cytoreduction with the use of somatostatin analogues. Somatostatin have a broad range of biological actions that include inhibition of exocrine and endocrine secretions, gut motility, cell proliferation, cell survival and angiogenesis...
April 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28496188/preclinical-evaluation-of-pac1-targeting-with-radiolabeled-maxadilan
#11
Lieke Joosten, Maarten Brom, Martin K H Schäfer, Otto C Boerman, Eberhard Weihe, Martin Gotthardt
There is an ongoing search for new tracers to optimize imaging of beta cell-derived tumors (insulinomas). The PAC1 receptor, expressed by insulinomas, can be used for targeting of these tumors. Here, we investigated whether radiolabeled maxadilan could be used for insulinoma imaging. Maxadilan was C- or N-terminally conjugated with DTPA (termed maxadilan-DPTA or DTPA-maxadilan respectively). BALB/c nude mice bearing subcutaneous INS-1 tumors were injected with either In-111-labeled maxadilan-DTPA or In-111-DTPA-maxadilan...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28491431/hyperinsulinaemic-hypoglycaemic-syndrome-due-to-acquired-nesidioblastosis-in-a-cat
#12
Lydia E Hambrook, Amanda A Ciavarella, Judith S Nimmo, Julie Wayne
Case summary A 6-year-old, neutered female British Shorthair cat presented with acute-onset weakness and mental dullness. Initially the cat was mildly hyperglycaemic (9.9 mmol/l; reference interval [RI] 3.3-6.7 mmol/l). Over the following 12 h the cat developed central blindness, tremors, intermittent seizures and opisthotonus. Repeat blood sampling revealed a marked hypoglycaemia (0.8 mmol/l). Insulin level (performed on a serum sample collected while the cat was hypoglycaemic) was inappropriately elevated (1575 mIU/l; RI 10-80 mIU/l)...
July 2016: JFMS Open Rep
https://www.readbyqxmd.com/read/28472826/t372r-mutation-status-in-yin-yang-1-gene-in-insulinoma-patients
#13
Khushboo Irshad, Viveka P Jyotsna, Shipra Agarwal, Kunzang Chosdol, Sujoy Pal, Rakesh Kumar Deepak
Insulinomas are rare pancreatic neuroendocrine tumors. The genetic causes underlying insulinoma are still being investigated. Recently, 3 independent studies reported a recurrent somatic mutation in YY1 gene (C>G; Thr372Arg) among insulinoma patients belonging to Chinese and Western Caucasian populations, which was found to increase insulin secretion by β-cells. However, the status of this key gene variation remains unknown in patients of other ethnicities. We, therefore, screened Indian sporadic insulinoma patients for YY1 T372R mutation in the present study...
May 4, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28467202/a-rationally-designed-peptide-ia-2-p2-against-type-1-diabetes-in-streptozotocin-induced-diabetic-mice
#14
Lili Shen, Shiping Lu, Dongcheng Huang, Guoliang Li, Kunfeng Liu, Rongyue Cao, Li Zong, Liang Jin, Jie Wu
Recent studies have investigated the potential of type 1 diabetes mellitus-related autoantigens, such as heat shock protein 60, to induce immunological tolerance or to suppress the immune response. A functional 24-residue peptide derived from heat shock protein 60 (P277) has shown anti-type 1 diabetes mellitus potential in experimental animals and in clinical studies, but it also carries a potential atherogenic effect. In this study, we have modified P277 to retain an anti-type 1 diabetes mellitus effect and minimize the atherogenic potential by replacing the P277 B epitope with another diabetes-associated autoantigen, insulinoma antigen-2 (IA-2), to create the fusion peptide IA-2-P2...
May 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28465532/demonstration-of-interposed-modular-hydrogel-sheet-for-multicellular-analysis-in-a-microfluidic-assembly-platform
#15
Chae Yun Bae, Jaejung Son, Hail Kim, Je-Kyun Park
Hydrogel sheets have emerged as a promising biomaterial scaffold for the encapsulation and transfer of multicellular structures. Although the improvement of the chemical interactions and the design of micro-scaled geometry have contributed to the development of multipurpose hydrogel scaffolds, the application of hydrogel sheets to assess multicellular structures is still challenging. To expand the technical applicability of hydrogel sheets, we here demonstrate that a single layer of the hydrogel sheet can be integrated as an interposed module in a microfluidic device for multicellular analysis...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28462560/seizures-due-to-insulinoma-a-rare-but-treatable-cause
#16
Shubha Bhalla, Vps Punia, M Narang, Pushpa Kumari, Saurabh Gupta
Hypoglycemia can cause multiple neuroglycopenic symptoms; seizures being one of them. Misdiagnosis and delay in treatment are common and prolonged hypoglycemia can lead to permanent neurological deficit or fatal coma. Hypoglycemia caused by an insulinoma is a readily treatable condition that should be considered in the differential diagnosis of intractable seizures. The following case report highlights the need for careful reassessment of all seizures that are atypical and refractory to medication.
March 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28458908/endoscopic-ultrasound-guided-ethanol-ablation-therapy-for-pancreatic-insulinoma-an-unusual-strategy
#17
Adriana de Sousa Lages, Isabel Paiva, Patrícia Oliveira, Francisco Portela, Francisco Carrilho
SUMMARY: Insulinomas are the most frequent cause of hyperinsulinaemic hypoglycaemia. Although surgical enucleation is the standard treatment, a few other options are available to high-risk patients who are elderly or present with co-morbidities. We present a case report of an 89-year-old female patient who was admitted to the emergency department due to recurrent hypoglycaemia, especially during fasting. Laboratory work-up raised the suspicion of hyperinsulinaemic hypoglycaemia, and abdominal CT scan revealed a 12 mm nodular hypervascular lesion of the pancreatic body suggestive of neuroendocrine tumour...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28449948/sunitinib-specifically-augments-glucose-induced-insulin-secretion
#18
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
#19
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
#20
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
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