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Pancreatic beta cells

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https://www.readbyqxmd.com/read/29686779/valproic-acid-exposure-of-pregnant-rats-during-organogenesis-disturbs-pancreas-development-in-insulin-synthesis-and-secretion-of-the-offspring
#1
Komariah Komariah, Wasmen Manalu, Bambang Kiranadi, Adi Winarto, Ekowati Handharyani, M Orliando Roeslan
Valproic acid (VPA) plays a role in histone modifications that eventually inhibit the activity of histone deacetylase (HDAC), and will affect the expressions of genes Pdx1, Nkx6.1, and Ngn3 during pancreatic organogenesis. This experiment was designed to study the effect of VPA exposure in pregnant rats on the activity of HDAC that controls the expression of genes regulating the development of beta cells in the pancreas to synthesize and secrete insulin. This study used 30 pregnant Sprague-Dawley rats, divided into 4 groups, as follows: (1) a control group of pregnant rats without VPA administration, (2) pregnant rats administered with 250 mg VPA on day 10 of pregnancy, (3) pregnant rats administered with 250 mg VPA on day 13 of pregnancy, and (4) pregnant rats administered with 250 mg VPA on day 16 of pregnancy...
April 2018: Toxicological Research
https://www.readbyqxmd.com/read/29686402/targeting-glp-1-receptor-trafficking-to-improve-agonist-efficacy
#2
Ben Jones, Teresa Buenaventura, Nisha Kanda, Pauline Chabosseau, Bryn M Owen, Rebecca Scott, Robert Goldin, Napat Angkathunyakul, Ivan R Corrêa, Domenico Bosco, Paul R Johnson, Lorenzo Piemonti, Piero Marchetti, A M James Shapiro, Blake J Cochran, Aylin C Hanyaloglu, Asuka Inoue, Tricia Tan, Guy A Rutter, Alejandra Tomas, Stephen R Bloom
Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic beta cells, causes weight loss, and is an important pharmacological target in type 2 diabetes (T2D). Like other G protein-coupled receptors, the GLP-1R undergoes agonist-mediated endocytosis, but the functional and therapeutic consequences of modulating GLP-1R endocytic trafficking have not been clearly defined. Here, we investigate a series of biased GLP-1R agonists with variable propensities for GLP-1R internalization and recycling...
April 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29681182/fetal-pancreatic-langerhans-islets-size-in-pregnancies-with-metabolic-disorders
#3
Laura Avagliano, Margaret Mascherpa, Valentina Massa, Patrizia Doi, Gaetano P Bulfamante
Metabolic disorders are a pandemic and increasing health problem. Women of childbearing age may also be affected, thus an abnormal metabolism may interfere with pregnancy short and long term outcomes, harming both mother and child. In the context of an abnormal maternal and intrauterine metabolic milieu the development of fetal organs, including pancreas, may be affected. The aim of the present study is to investigate the effects of pregnancy metabolic disorders on the morphology of pancreatic Langerhans islets in human late-third trimester stillborn fetuses...
April 22, 2018: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29678908/the-lim-homeodomain-protein-isl1-mediates-the-function-of-tcf7l2-in-pancreatic-beta-cells
#4
Weijuan Shao, Vivian Szeto, Zhuolun Song, Lili Tian, Zhong-Ping Feng, Cristina M Nostro, Tianru Jin
Pancreatic β-cell Tcf7l2 deletion or its functional knockdown suggested the essential role of this Wnt pathway effector in controlling insulin secretion, glucose homeostasis, and β-cell gene expression. As the LIM homeodomain protein Isl1 is a suggested Wnt pathway downstream target, we hypothesize that it mediates metabolic functions of Tcf7l2. We aimed to determine the role of Isl1 in mediating the function of Tcf7l2 and the incretin hormone GLP-1 in pancreatic β-cells. Effect of dominant negative TCF7L2 (TCF7L2DN) mediated Wnt pathway functional knockdown on Isl1 expression was determined in βTCFDN mouse islets and in the rat insulinoma cell line INS-1 832/13...
April 20, 2018: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29675567/human-urine-derived-stem-cells-play-a-novel-role-in-the-treatment-of-stz-induced-diabetic-mice
#5
Tianxue Zhao, Deng Luo, Yun Sun, Xin Niu, Yang Wang, Chen Wang, Weiping Jia
Human urine-derived stem cells (hUSCs) are a potential stem cell source for cell therapy. However, the effect of hUSCs on glucose metabolism regulation in type 1 diabetes was not clear. Therefore, the aim of the study was to evaluate whether hUSCs have protective effect on streptozotocin (STZ)-induced diabetes. hUSCs were extracted and cultivated with a special culture medium. Flow cytometry analysis was applied to detect cell surface markers. BALB/c male nude mice were either injected with high-dose STZ (HD-STZ) or multiple low-dose STZ (MLD-STZ)...
April 19, 2018: Journal of Molecular Histology
https://www.readbyqxmd.com/read/29675560/patterns-of-differential-gene-expression-in-a-cellular-model-of-human-islet-development-and-relationship-to-type-2-diabetes-predisposition
#6
Marta Perez-Alcantara, Christian Honoré, Agata Wesolowska-Andersen, Anna L Gloyn, Mark I McCarthy, Mattias Hansson, Nicola L Beer, Martijn van de Bunt
AIMS/HYPOTHESIS: Most type 2 diabetes-associated genetic variants identified via genome-wide association studies (GWASs) appear to act via the pancreatic islet. Observed defects in insulin secretion could result from an impact of these variants on islet development and/or the function of mature islets. Most functional studies have focused on the latter, given limitations regarding access to human fetal islet tissue. Capitalising upon advances in in vitro differentiation, we characterised the transcriptomes of human induced pluripotent stem cell (iPSC) lines differentiated along the pancreatic endocrine lineage, and explored the contribution of altered islet development to the pathogenesis of type 2 diabetes...
April 19, 2018: Diabetologia
https://www.readbyqxmd.com/read/29675259/successful-neoadjuvant-peptide-receptor-radionuclide-therapy-for-an-inoperable-pancreatic-neuroendocrine-tumour
#7
Tiago Nunes da Silva, M L F van Velthuysen, Casper H J van Eijck, Jaap J Teunissen, J Hofland, Wouter W de Herder
Non-functional pancreatic neuroendocrine tumours (NETs) can present with advanced local or distant (metastatic) disease limiting the possibility of surgical cure. Several treatment options have been used in experimental neoadjuvant settings to improve the outcomes in such cases. Peptide receptor radionuclide therapy (PPRT) using beta emitting radiolabelled somatostatin analogues has been used in progressive pancreatic NETs. We report a 55-year-old female patient with a 12.8 cm pancreatic NET with significant local stomach and superior mesenteric vein compression and liver metastases...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29673066/total-pancreaticoduodenectomy-with-autologous-islet-transplantation-fourteen-years-after-liver-contained-composite-visceral-transplantation
#8
Ahmed Nassar, Cristiano Quintini, Guilherme Costa, Elizabeth Lennon, Rita Bottino, Betul Hatipoglu, Koji Hashimoto, Masato Fujiki, Fouad Kandeel, R Matthew Walsh, Kareem Abu-Elmagd
Chronic pancreatitis (CP) is a severely disabling disorder with potential detrimental effects on quality of life, gut function, and glucose homeostasis. Disease progression often results in irreversible morphological and functional abnormalities with development of chronic pain, mechanical obstruction, and pancreatic insufficiency. Along with comprehensive medical management, the concept of total pancreatectomy and islet autotransplantation (TP-AIT) was introduced forty years ago for patients with intractable pain and preserved beta-cell function...
April 19, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29671418/the-role-of-k-atp-channels-in-cerebral-ischemic-stroke-and-diabetes
#9
REVIEW
Vivian Szeto, Nai-Hong Chen, Hong-Shuo Sun, Zhong-Ping Feng
ATP-sensitive potassium (KATP ) channels are ubiquitously expressed on the plasma membrane of cells in multiple organs, including the heart, pancreas and brain. KATP channels play important roles in controlling and regulating cellular functions in response to metabolic state, which are inhibited by ATP and activated by Mg-ADP, allowing the cell to couple cellular metabolic state (ATP/ADP ratio) to electrical activity of the cell membrane. KATP channels mediate insulin secretion in pancreatic islet beta cells, and controlling vascular tone...
April 19, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29671177/tri-modal-in-vivo-imaging-of-pancreatic-islets-transplanted-subcutaneously-in-mice
#10
Sayuan Liang, Karim Louchami, Bryan Holvoet, Rein Verbeke, Christophe M Deroose, Bella Manshian, Stefaan J Soenen, Ine Lentacker, Uwe Himmelreich
PURPOSE: Transplantation of pancreatic islets (PIs) is a promising therapeutic approach for type 1 diabetes. The main obstacle for this strategy is that the outcome of islet engraftment depends on the engraftment site. It was our aim to develop a strategy for using non-invasive imaging techniques to assess the location and fate of transplanted PIs longitudinally in vivo. PROCEDURES: In order to overcome the limitations of individual imaging techniques and cross-validate findings by different modalities, we have combined fluorine magnetic resonance imaging (F-19 MRI), fluorescence imaging (FLI), and bioluminescent imaging (BLI) for studying subcutaneously transplanted PIs and beta cell-like cells (INS-1E cell line) in vivo...
April 18, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29671131/diabetes-in-south-asians-phenotype-clinical-presentation-and-natural-history
#11
REVIEW
Ranjit Unnikrishnan, Prasanna Kumar Gupta, Viswanathan Mohan
PURPOSE OF REVIEW: South Asia is one of the epicenters of the global diabetes pandemic. Diabetes in south Asians has certain peculiar features with respect to its pathophysiology, clinical presentation, and management. This review aims to summarize some of the recent evidence pertaining to the distinct diabetes phenotype in south Asians. RECENT FINDINGS: South Asia has high incidence and prevalence rates of diabetes. The progression from "pre-diabetes" to diabetes also occurs faster in this population...
April 18, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29671030/abnormal-islet-sphingolipid-metabolism-in-type-1-diabetes
#12
Laurits J Holm, Lars Krogvold, Jane P Hasselby, Simranjeet Kaur, Laura A Claessens, Mark A Russell, Clayton E Mathews, Kristian F Hanssen, Noel G Morgan, Bobby P C Koeleman, Bart O Roep, Ivan C Gerling, Flemming Pociot, Knut Dahl-Jørgensen, Karsten Buschard
AIMS/HYPOTHESIS: Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice. METHODS: We examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy...
April 18, 2018: Diabetologia
https://www.readbyqxmd.com/read/29670917/pancreatic-beta-cell-death-novel-potential-mechanisms-in-diabetes-therapy
#13
REVIEW
Joselyn Rojas, Valmore Bermudez, Jim Palmar, María Sofía Martínez, Luis Carlos Olivar, Manuel Nava, Daniel Tomey, Milagros Rojas, Juan Salazar, Carlos Garicano, Manuel Velasco
Purpose of Review: Describing the diverse molecular mechanisms (particularly immunological) involved in the death of the pancreatic beta cell in type 1 and type 2 diabetes mellitus. Recent Findings: Beta cell death is the final event in a series of mechanisms that, up to date, have not been entirely clarified; it represents the pathophysiological mechanism in the natural history of diabetes mellitus. These mechanisms are not limited to an apoptotic process only, which is characteristic of the immune-mediated insulitis in type 1 diabetes mellitus...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29663654/nifurpirinol-a-more-potent-and-reliable-substrate-compared-to-metronidazole-for-nitroreductase-mediated-cell-ablations
#14
David Bergemann, Laura Massoz, Jordane Bourdouxhe, Claudio A Carril Pardo, Marianne L Voz, Bernard Peers, Isabelle Manfroid
The zebrafish is a popular animal model with well-known regenerative capabilities. To study regeneration in this fish, the nitroreductase/metronidazole-mediated system is widely used for targeted ablation of various cell types. Nevertheless, we highlight here some variability in ablation efficiencies with the metronidazole prodrug that led us to search for a more efficient and reliable compound. Herein, we present nifurpirinol, another nitroaromatic antibiotic, as a more potent prodrug compared to metronidazole to trigger cell-ablation in nitroreductase expressing transgenic models...
April 17, 2018: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/29662071/lrh-1-agonism-favours-an-immune-islet-dialogue-which-protects-against-diabetes-mellitus
#15
Nadia Cobo-Vuilleumier, Petra I Lorenzo, Noelia García Rodríguez, Irene de Gracia Herrera Gómez, Esther Fuente-Martin, Livia López-Noriega, José Manuel Mellado-Gil, Silvana-Yanina Romero-Zerbo, Mathurin Baquié, Christian Claude Lachaud, Katja Stifter, German Perdomo, Marco Bugliani, Vincenzo De Tata, Domenico Bosco, Geraldine Parnaud, David Pozo, Abdelkrim Hmadcha, Javier P Florido, Miguel G Toscano, Peter de Haan, Kristina Schoonjans, Luis Sánchez Palazón, Piero Marchetti, Reinhold Schirmbeck, Alejandro Martín-Montalvo, Paolo Meda, Bernat Soria, Francisco-Javier Bermúdez-Silva, Luc St-Onge, Benoit R Gauthier
Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis...
April 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29659906/increased-chromogranin-a-positive-hormone-negative-cells-in-chronic-pancreatitis
#16
Abu Saleh Md Moin, Megan Cory, Jennifer Choi, Allison Ong, Sangeeta Dhawan, Sarah M Dry, Peter Butler, Robert Rizza, Alexandra Butler
Context: Chronic pancreatitis (CP) is characterized by inflammation, fibrosis and a loss of pancreatic acinar cells which can result in exocrine and eventually endocrine deficiency. Pancreatitis has been reported to induce formation of new endocrine cells (neogenesis) in mice. Our recent data has implicated Chromogranin A-positive hormone negative (CPHN) cells as potential evidence of neogenesis in humans. Objective: We sought to establish if CPHN cells were more abundant in chronic pancreatitis in humans...
April 5, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29627323/apoptosis-signal-regulating-kinase-1-and-nadph-oxidase-mediate-human-amylin-evoked-redox-stress-and-apoptosis-in-pancreatic-beta-cells
#17
Sanghamitra Singh, Diti Chatterjee Bhowmick, Satyabrata Pany, Myungkuk Joe, Noor Zaghlula, Aleksandar M Jeremic
Misfolded toxic human islet amyloid polypeptide or amylin (hA) and plasma membrane-associated redox complex, NADPH oxidase (NOX), have been implicated in the islet β-cell demise associated with type-2 diabetes mellitus (T2DM). Studies show that hA accumulation is stressful to β-cells and that misfolding of human amylin evokes redox stress and activates mitogen activated protein (MAP) kinases, p38 MAPK and c-Jun N-terminal (JNK) kinase. However, the molecular link and causality between hA-evoked redox stress, NOX activity and MAP kinases signaling in pancreatic β-cells is incompletely understood...
April 5, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29627317/intestinal-cart-is-a-regulator-of-gip-and-glp-1-secretion-and-expression
#18
L Shcherbina, A Lindqvist, A-H Thorén Fischer, E Ahlqvist, E Zhang, S E Falkmer, E Renström, J Koffert, H Honka, N Wierup
Impaired incretin effect is a culprit in Type 2 Diabetes. Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide controlling pancreatic islet hormone secretion and beta-cell survival. Here we studied the potential expression of CART in enteroendocrine cells and examined the role of CART as a regulator of incretin secretion and expression. CART expression was found in glucose-dependent insulinotropic polypeptide (GIP)-producing K-cells and glucagon-like peptide-1 (GLP-1)-producing L-cells in human duodenum and jejunum and CART levels were increased 60 min after a meal in humans...
April 5, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29624168/age-related-islet-inflammation-marks-the-proliferative-decline-of-pancreatic-beta-cells-in-zebrafish
#19
Sharan Janjuha, Sumeet Pal Singh, Anastasia Tsakmaki, Neda Mousavy-Gharavy, Priyanka Murawala, Judith Konantz, Sarah Birke, David J Hodson, Guy Rutter, Gavin Bewick, Nikolay N Ninov
The pancreatic islet, a cellular community harboring the insulin-producing beta-cells, is known to undergo age-related alterations. However, only a handful of signals associated with aging have been identified. By comparing beta-cells from younger and older zebrafish, here we show that the aging islets exhibit signs of chronic inflammation. These include recruitment of tnfα -expressing macrophages and the activation of NF-kB signaling in beta-cells. Using a transgenic reporter, we show that NF-kB activity is undetectable in juvenile beta-cells, whereas cells from older fish exhibit heterogeneous NF-kB activity...
April 6, 2018: ELife
https://www.readbyqxmd.com/read/29623227/fulminant-diabetes-in-a-patient-with-advanced-melanoma-on-nivolumab
#20
Nora Chokr, Hafsa Farooq, Elizabeth Guadalupe
Background: Anti-PD-1 agents were approved for advanced melanoma after the landmark trial Checkmate-037. Anti-PD-1 agents can breach immunologic tolerance. Fulminant diabetes is an immune endocrinopathy that results from a violent immune attack leading to complete destruction of pancreatic beta cells in genetically predisposed people. We present a rare case of fulminant diabetes precipitated by anti-PD-1 immunotherapy. Case: A 61-year-old male with advanced melanoma presented with a three-day history of nausea, vomiting, and malaise...
2018: Case Reports in Oncological Medicine
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