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Pancreas islet

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https://www.readbyqxmd.com/read/29339498/mafa-missense-mutation-causes-familial-insulinomatosis-and-diabetes-mellitus
#1
Donato Iacovazzo, Sarah E Flanagan, Emily Walker, Rosana Quezado, Fernando Antonio de Sousa Barros, Richard Caswell, Matthew B Johnson, Matthew Wakeling, Michael Brändle, Min Guo, Mary N Dang, Plamena Gabrovska, Bruno Niederle, Emanuel Christ, Stefan Jenni, Bence Sipos, Maike Nieser, Andrea Frilling, Ketan Dhatariya, Philippe Chanson, Wouter W de Herder, Björn Konukiewitz, Günter Klöppel, Roland Stein, Márta Korbonits, Sian Ellard
The β-cell-enriched MAFA transcription factor plays a central role in regulating glucose-stimulated insulin secretion while also demonstrating oncogenic transformation potential in vitro. No disease-causing MAFA variants have been previously described. We investigated a large pedigree with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we identified a missense MAFA mutation (p...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29338388/novel-fusion-protein-targeting-mitochondrial-dna-improves-pancreatic-islet-functional-potency-and-islet-transplantation-outcomes
#2
Juan S Danobeitia, Peter J Chlebeck, Inna Shokolenko, Xiaobo Ma, Glenn Wilson, Luis A Fernandez
Long-term graft survival is an ongoing challenge in the field of islet transplantation. With the growing demand for transplantable organs, therapies to improve organ quality and reduce the incidence of graft dysfunction are of paramount importance. We evaluated the protective role of a recombinant DNA repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent using a rodent model of pancreatic islet transplantation. We first investigated the effect of therapy on isolated rat islets cultured with pro-inflammatory cytokines (interleukin-1 β, interferon γ, and tumor necrosis factor α) for 48 h and documented a significant reduction in apoptosis by flow cytometry, improved viability by immunofluorescence, and conserved functional potency in vitro and in vivo in Exscien I-III-treated islets...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29338387/quantifying-the-effects-of-different-neutral-proteases-on-human-islet-integrity
#3
Heide Brandhorst, Paul R V Johnson, Olle Korsgren, Daniel Brandhorst
Efficient islet release from the pancreas requires the combination of collagenase, neutral protease (cNP), or thermolysin (TL). Recently, it has been shown that clostripain (CP) may also contribute to efficient islet release from the human pancreas. The aim of this study was to evaluate the impact of these proteases on human islet integrity in a prospective approach. Islets were isolated from the pancreas of 10 brain-dead human organ donors. Purified islets were precultured for 3 to 4 d at 37 °C to ensure that preparations were cleared of predamaged islets, and only integral islets were subjected to 90 min of incubation at 37 °C in Hank's balanced salt solution supplemented with cNP, TL, or CP...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29337308/rage-binds-preamyloid-iapp-intermediates-and-mediates-pancreatic-%C3%AE-cell-proteotoxicity
#4
Andisheh Abedini, Ping Cao, Annette Plesner, Jinghua Zhang, Meilun He, Julia Derk, Sachi A Patil, Rosa Rosario, Jacqueline Lonier, Fei Song, Hyunwook Koh, Huilin Li, Daniel P Raleigh, Ann Marie Schmidt
Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid polypeptide (IAPP) in pancreatic islets, resulting in β cell toxicity, which exacerbates type 2 diabetes and islet transplant failure. It is not fully clear how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or treated. We recently defined the properties of toxic IAPP species. Here, we have identified a receptor-mediated mechanism of islet amyloidosis-induced proteotoxicity. In human diabetic pancreas and in cellular and mouse models of islet amyloidosis, increased expression of the receptor for advanced glycation endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) β cell and islet inflammation, toxicity, and apoptosis...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29335884/effects-of-moderate-exercise-on-biochemical-morphological-and-physiological-parameters-of-the-pancreas-of-female-mice-with-estrogen-deprivation-and-dyslipidemia
#5
Aparecida Gabriela Bexiga Veloso, Nathalia Edviges Alves Lima, Elisabete de Marco Ornelas, Clever Gomes Cardoso, Mara Rubia Marques, Beatriz da Costa Aguiar Alves Reis, Fernando Luiz Affonso Fonseca, Laura Beatriz Mesiano Maifrino
Menopausal women are at high risk of developing heart disease. However, physical exercise practice can reverse this scenario. We evaluated the biochemical, morphological, and physiological effects of moderate aerobic physical exercise on the pancreas of knockout mice for LDL receptor with estrogen deprivation by ovariectomy. Animals were divided into six groups (n = 5): sedentary non-ovariectomized control; sedentary ovariectomized control; trained ovariectomized control; sedentary non-ovariectomized LDL-R knockout; sedentary ovariectomized LDL-R knockout; and trained ovariectomized LDL-R knockout...
January 15, 2018: Medical Molecular Morphology
https://www.readbyqxmd.com/read/29335487/increased-expression-of-glp-1r-in-proliferating-islets-of-men1-mice-is-detectable-by-68ga-ga-do3a-vs-cys40-exendin-4-pet
#6
Azita Monazzam, Joey Lau, Irina Velikyan, Su-Chen Li, Masoud Razmara, Ulrika Rosenström, Olof Eriksson, Britt Skogseid
Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29333050/improvement-of-insulin-secretion-and-pancreatic-%C3%AE-cell-function-in-streptozotocin-induced-diabetic-rats-treated-with-aloe-vera-extract
#7
Ayesha Noor, S Gunasekaran, M A Vijayalakshmi
Background: Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia. Plant extracts and their products are being used as an alternative system of medicine for the treatment of diabetes. Aloe vera has been traditionally used to treat several diseases and it exhibits antioxidant, anti-inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar diabetic rats were used in this study to understand the potential protective effect of A. vera extract on the pancreatic islets...
December 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/29331269/clinical-benefits-of-autologous-haematopoietic-stem-cell-transplantation-in-type-1-diabetes-patients
#8
B Gu, H Miao, J Zhang, J Hu, W Zhou, W Gu, W Wang, G Ning
Type 1 diabetes (T1D) is characterized by severe damage to pancreas islet function through immunological attack; therefore, it is also called 'insulin-dependent diabetes'. The present study aimed to evaluate the safety and clinical efficacy of autologous haematopoietic stem cell transplantation (AHSCT) in adolescent patients with newly diagnosed T1D. A phase-II prospective, parallel-assignment, non-randomized trial was conducted from March 2008 to December 2011 with 40 T1D patients, of whom 20 received AHSCT therapy and 20 were treated only with insulin injections...
December 22, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29330353/afadin-and-rhoa-control-pancreatic-endocrine-mass-via-lumen-morphogenesis
#9
D Berfin Azizoglu, Caitlin Braitsch, Denise K Marciano, Ondine Cleaver
Proper lumen morphogenesis during pancreas development is critical to endocrine and exocrine cell fate. Recent studies showed that a central network of lumens (termed core), but not the surrounding terminal branches (termed periphery), produces most islet endocrine cells. To date, it remains unclear how pancreatic lumens form and remodel and which aspects of lumen morphogenesis influence cell fate. Importantly, models testing the function of the central lumen network as an endocrine niche are lacking. Here, we identify mechanisms underlying lumen formation and remodeling and show that central lumen network morphogenesis impacts pancreatic endocrine mass...
January 12, 2018: Genes & Development
https://www.readbyqxmd.com/read/29321828/exendin-4-protects-mice-from-d-galactose-induced-hepatic-and-pancreatic-dysfunction
#10
Akram Ahangarpour, Ali Akbar Oroojan, Mohammad Badavi
Investigations into pharmaceutical intervention of pancreatic and hepatic dysfunction associated with metabolic disturbances have received relatively little attention. The aim of this study was to investigate the protective effects of exendin-4 in mice receiving D-galactose, a reducing sugar that triggers ROS production and inflammatory mediators affecting the pancreas and liver. Exendin-4 is an United States Food and Drug Administration (FDA) approved glucagon-like peptide that increases insulin dependent glycogen synthesis and glucose uptake...
2018: Pathobiology of Aging & Age related Diseases
https://www.readbyqxmd.com/read/29320541/agent-based-modeling-of-the-interaction-between-cd8-t-cells-and-beta-cells-in-type-1-diabetes
#11
Mustafa Cagdas Ozturk, Qian Xu, Ali Cinar
We propose an agent-based model for the simulation of the autoimmune response in T1D. The model incorporates cell behavior from various rules derived from the current literature and is implemented on a high-performance computing system, which enables the simulation of a significant portion of the islets in the mouse pancreas. Simulation results indicate that the model is able to capture the trends that emerge during the progression of the autoimmunity. The multi-scale nature of the model enables definition of rules or equations that govern cellular or sub-cellular level phenomena and observation of the outcomes at the tissue scale...
2018: PloS One
https://www.readbyqxmd.com/read/29319366/effects-of-subchronic-acrylamide-treatment-on-the-endocrine-pancreas-of-juvenile-male-wistar-rats
#12
M Stošić, M Matavulj, J Marković
Acrylamide (AA) is a well-known industrial monomer with carcinogenic, mutagenic, neurotoxic and endocrine disruptive effects on living organisms. AA has been the subject of renewed interest owing to its presence in various food products. We investigated the potential adverse effects of oral AA treatment on the endocrine pancreas of juvenile rats using histochemical, immunohistochemical, stereological and biochemical methods. Thirty juvenile male Wistar rats were divided into one control and two AA treatment groups: one treated with 25 mg/kg AA and the other treated with 50 mg/kg AA for 21 days...
January 10, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29319179/muscle-derived-satellite-cells-for-treating-type-1-diabetes-in-rats-rattus-norvegicus
#13
Yu Ren, Hefei Wang, Si Ha, Xingsheng Zhao, Xiao Wang, Yu Lan, Xiaoling Liu
Diabetes mellitus(DM) is a complicated metabolic disease, with the fundamental treatment nowadays being diet control, insulin injections, slet or pancreas transplantation, which is limited because exogenous insulin injections fail to simulate normal insulin secretion in islet beta cells successfully and islet transplantation lacks organ donors. So far, stem cells with highly self-renewal and multi-directional differentiation potential have become a new hope for the treatment of diabetes. In this research, rat Muscle-derived satellite cells *MDSCs*were separated and cultivated in vitro and inducted into insulin-producing cells with observation and identification using dithizone staining and so on...
January 10, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29315753/localization-of-amylin-like-immunoreactivity-in-the-striped-velvet-gecko-pancreas
#14
H Suzuki, T Yamamoto
Immunohistochemical techniques were employed to investigate the distribution of amylin-like immunoreactive cells in the pancreas of gecko Homopholis fasciata. Four types of endocrine cells were distinguished: insulin immunoreactive (B cells), pancreatic polypeptide immunoreactive (PP cells), glucagon and pancreatic polypeptide immunoreactive (A/PP cells) and somatostatin immunoreactive cells (D cells). Pancreatic islets contained B, A/PP and D cells, whereas extrainsular regions contained B, D and PP cells...
January 8, 2018: Anatomia, Histologia, Embryologia
https://www.readbyqxmd.com/read/29315020/systematic-review-of-islet-cryopreservation
#15
Greg G Kojayan, Michael Alexander, David K Imagawa, Jonathan R T Lakey
Pancreatic islet transplantation is being extensively researched as an alternative treatment for type 1 diabetic patients. This treatment is currently limited by temporal mismatch, between the availability of pancreas and isolated islets from deceased organ donor, and the recipient's need for freshly isolated islets. To solve this issue, cryopreservation of islets may offer the potential to bank islets for transplant on demand. Cryopreservation, however, introduces an overwhelmingly harsh environment to the ever-so-fragile islets...
January 9, 2018: Islets
https://www.readbyqxmd.com/read/29314619/naringin-protects-pancreatic-%C3%AE-cells-against-oxidative-stress-induced-apoptosis-by-inhibiting-both-intrinsic-and-extrinsic-pathways-in-insulin-deficient-diabetic-mice
#16
Ye Jin Lim, Jung Ho Kim, Jeong Hoon Pan, Jae Kyeom Kim, Tae-Sik Park, Young Jun Kim, Jin Hyup Lee, Jun Ho Kim
SCOPE: Oxidative stress has been suggested to play a central role in the pathogenesis of diabetes, as well as other metabolic disorders. Naringin, a major flavanone glycoside in citrus species, has been shown to display strong antioxidant potential in in vitro and in vivo models of oxidative stress; however, the underlying protective mechanisms in diabetes are unclear. METHODS AND RESULTS: To study the protective effects and molecular mechanisms of naringin in preventing islet dysfunction and diabetes, we examined glucose homeostasis, β-cell apoptosis, and inflammatory response in insulin-deficient diabetic mice exposed to acute oxidative stress with streptozotocin (STZ)...
January 4, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29311365/simultaneous-recognition-of-allogeneic-mhc-and-cognate-autoantigen-by-autoreactive-t-cells-in-transplant-rejection
#17
Adam L Burrack, Laurie G Landry, Janet Siebert, Marilyne Coulombe, Ronald G Gill, Maki Nakayama
The autoimmune condition is a primary obstacle to inducing tolerance in type 1 diabetes patients receiving allogeneic pancreas transplants. It is unknown how autoreactive T cells that recognize self-MHC molecules contribute to MHC-disparate allograft rejection. In this report, we show the presence and accumulation of dual-reactive, that is autoreactive and alloreactive, T cells in C3H islet allografts that were transplanted into autoimmune diabetic NOD mice. Using high-throughput sequencing, we discovered that T cells prevalent in allografts share identical TCRs with autoreactive T cells present in pancreatic islets...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29310936/the-rhogap-stard13-controls-insulin-secretion-through-f-actin-remodeling
#18
Heike Naumann, Thomas Rathjen, Matthew N Poy, Francesca M Spagnoli
OBJECTIVE: Actin cytoskeleton remodeling is necessary for glucose-stimulated insulin secretion in pancreatic β-cells. A mechanistic understanding of actin dynamics in the islet is paramount to a better comprehension of β-cell dysfunction in diabetes. Here, we investigate the Rho GTPase regulator Stard13 and its role in F-actin cytoskeleton organization and islet function in adult mice. METHODS: We used Lifeact-EGFP transgenic animals to visualize actin cytoskeleton organization and dynamics in vivo in the mouse islets...
December 28, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29306997/extracellular-matrix-molecules-and-their-potential-contribution-to-the-function-of-transplanted-pancreatic-islets
#19
REVIEW
L Alberto Llacua, Marijke M Faas, Paul de Vos
Extracellular matrix (ECM) molecules are responsible for structural and biochemical support, as well as for regulation of molecular signalling and tissue repair in many organ structures, including the pancreas. In pancreatic islets, collagen type IV and VI, and laminins are the most abundant molecules, but other ECM molecules are also present. The ECM interacts with specific combinations of integrin α/β heterodimers on islet cells and guides many cellular processes. More specifically, some ECM molecules are involved in beta cell survival, function and insulin production, while others can fine tune the susceptibility of islet cells to cytokines...
January 6, 2018: Diabetologia
https://www.readbyqxmd.com/read/29301189/congenital-hyperinsulinism-diagnostic-and-management-challenges-in-a-developing-country-case-report
#20
Cheri Mathews John, Prakash Agarwal, Suriyakumar Govindarajulu, Sandhya Sundaram, Senthil Senniappan
Management of congenital hyperinsulinemia of infancy (CHI) is challenging. A 4-month-old female infant with persistent hypoglycemia and elevated insulin levels was diagnosed with CHI. Gallium-68 DOTANOC positron emission tomography/computed tomography (PET/CT) scan (68Ga-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid]-1-NaI3-octreotide) demonstrated focal disease in the body of the pancreas. Genetic studies indicated paternal inheritance, making focal disease likely. She was started on diazoxide therapy with partial improvement in blood glucose levels...
December 2017: Annals of Pediatric Endocrinology & Metabolism
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