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https://www.readbyqxmd.com/read/28649880/understanding-type-1-diabetes-through-proteomics
#1
Inne Crèvecoeur, Saurabh Vig, Chantal Mathieu, Lut Overbergh
Auto-immunity against pancreatic beta-cells leads to an absolute shortage of the hormone insulin, resulting in hyperglycemia and the onset of type 1 diabetes (T1D). Proteomic approaches have been used to elucidate the mechanisms of beta-cell dysfunction and death. Areas covered: In the present review, we discuss discoveries in the beta-cell proteome that have contributed to better insights in the role of the beta-cell in T1D. Techniques, such as 2D-DIGE and MALDI imaging, together with new approaches for sample preparation, including laser capture microdissection and immunopeptidomics, have resulted in novel mechanistic insights in the pathogenesis of T1D...
June 26, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28648619/nuclear-import-of-glucokinase-in-pancreatic-beta-cells-is-mediated-by-a-nuclear-localization-signal-and-modulated-by-sumoylation
#2
Bente Berg Johansson, Karianne Fjeld, Marie Holm Solheim, Jun Shirakawa, Enming Zhang, Magdalena Keindl, Jiang Hu, Andreas Lindqvist, Anne Døskeland, Gunnar Mellgren, Torgeir Flatmark, Pål Rasmus Njølstad, Rohit N Kulkarni, Nils Wierup, Ingvild Aukrust, Lise Bjørkhaug
The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we here present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal ((30)LKKVMRR(36)) in the human enzyme...
June 22, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28646700/increased-serum-mir-7-is-a-promising-biomarker-for-type-2-diabetes-mellitus-and-its-microvascular-complications
#3
Shujun Wan, Jun Wang, Jing Wang, Jia Wu, Jiaxi Song, Chen-Yu Zhang, Chunni Zhang, Cheng Wang, Jun-Jun Wang
AIMS: To investigate the alteration pattern and physiologic state of islet-specific miR-7 in the serum of patients with type 2 diabetes mellitus (T2DM) and T2DM-associated microvascular complications (T2DMC) and to evaluate its clinical significance. METHODS: The levels of serum miR-7 were firstly examined and compared in 76 T2DM patients, 76 T2DMC patients and 74 age-gender matched controls using RT-qPCR. Subsequently, the physiologic state of serum miR-7 was characterized by determining its concentrations in isolated exosomes and corresponding exosome-free samples from the same three cohorts' samples...
June 11, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28632819/enzyme-development-for-human-islet-isolation-five-decades-of-progress-or-stagnation
#4
Daniel Brandhorst, Heide Brandhorst, Paul R V Johnson
In comparison to procedures used for the separation of individual cell types from other organs, the process of human pancreatic islet isolation aims to digest the pancreatic exocrine matrix completely without dispersing the individual cells within the endocrine cell cluster. This objective is unique within the field of tissue separation, and outlines the challenge of islet isolation to balance two opposing priorities. Although significant progress has been made in the characterization and production of enzyme blends for islet isolation, there are still numerous areas which require improvement...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28625982/the-novel-stress-survival-islet-2-ssi-2-predominantly-present-in-listeria-monocytogenes-strains-of-st121-is-involved-in-alkaline-and-oxidative-stress-response
#5
Eva Harter, Eva Maria Wagner, Andreas Zaiser, Sabrina Halecker, Martin Wagner, Kathrin Rychli
The food-borne pathogen Listeria (L) monocytogenes is able to survive a variety of stress conditions leading to the colonization of different niches like the food processing environment. This study focuses on the hypervariable genetic hotspot lmo0443-lmo0449 haboring three inserts: the stress survival islet 1 (SSI-1), the single-gene insert LMOf2365_0481 and two homologous genes of the non-pathogenic species L. innocua: lin0464, a putative transcriptional regulator and lin0465, an intracellular PfpI protease...
June 16, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28623288/seabirds-supply-nitrogen-to-reef-building-corals-on-remote-pacific-islets
#6
Anne Lorrain, Fanny Houlbrèque, Francesca Benzoni, Lucie Barjon, Laura Tremblay-Boyer, Christophe Menkes, David P Gillikin, Claude Payri, Hervé Jourdan, Germain Boussarie, Anouk Verheyden, Eric Vidal
Seabirds concentrate nutrients from large marine areas on their nesting islands playing an important ecological role in nutrient transfer between marine and terrestrial ecosystems. Here we investigate the role of guano on corals reefs across scales by analyzing the stable nitrogen isotopic (δ(15)N) values of the scleractinian coral Pocillopora damicornis on fringing reefs around two Pacific remote islets with large seabird colonies. Marine stations closest to the seabird colonies had higher nitrate + nitrite concentrations compared to more distant stations...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28612331/isolation-and-characterization-of-trophoblasts-from-enzymatic-explants-of-human-term-placenta
#7
Tamara D Kolokoltsova, Irina N Saburina, Irina M Zurina, Anastasia A Gorkun, Nastasia V Kosheleva, Vadim S Repin, Rimma A Poltavtseva, Gennady T Sukhikh
In the present study, we describe a new method of isolation and culture of human villous and extravillous trophoblasts from term placenta. The cultivation of trypsinized placental villous tissue explants, followed by the isolation of cells from outgrowth islets allows for obtaining a cytotrophoblast subpopulation that is free from contamination by other cell types. Compared to other methods, our protocol is mild, simple and effective, does not request costly reagents and provides isolation of the mononuclear cytotrophoblast cell populations free from contamination by other types of placental cells...
June 13, 2017: Human Cell
https://www.readbyqxmd.com/read/28605545/atypical-forms-of-congenital-hyperinsulinism-in-infancy-are-associated-with-mosaic-patterns-of-immature-islet-cells
#8
Bing Han, Zainab Mohamed, Maria Salomon Estebanez, Ross J Craigie, Melanie Newbould, Edmund Cheesman, Raja Padidela, Mars Skae, Matthew Johnson, Sarah Flanagan, Sian Ellard, Karen E Cosgrove, Indraneel Banerjee, Mark J Dunne
Objectives: We aimed to characterise mosaic populations of pancreatic islet cells from patients with atypical CHI (CHI-A) and the expression profile of NKX2.2, a key transcription factor expressed in β-cells but suppressed in δ-cells in the mature pancreas. Patients/Methods: Tissue was isolated from three patients with CHI-A following subtotal pancreatectomy. CHI-A was diagnosed on the basis of islet mosaicism and the absence of histopathological hallmarks of focal- and diffuse CHI (CHI-D)...
June 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28597607/immaturity-of-insulin-secretion-by-pancreatic-islets-isolated-from-one-human-neonate
#9
Jean-Claude Henquin, Myriam Nenquin
Human β-cells are functionally mature by the age of one year. The timing and mechanisms of this maturation are unknown owing to the exceptional availability of testable tissue. Here, we report the first in vitro study of insulin secretion by islets from a 5 day-old newborn. Glucose alone was inefficient but glucose-stimulation became concentration-dependent, displayed a biphasic time-course and was of similar magnitude as in infant islets when β-cell cAMP was raised by forskolin. Tolbutamide alone was effective in low glucose, but its effect was not augmented by high glucose...
June 8, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28584077/vascular-sprouts-induce-local-attraction-of-proangiogenic-neutrophils
#10
Gustaf Christoffersson, Jalal Lomei, Paul O'Callaghan, Johan Kreuger, Stefan Engblom, Mia Phillipson
Angiogenesis, the growth of new blood vessels, is a complex process requiring the orchestration of numerous different cell types, growth factors, and chemokines. Some of the recently acknowledged actors in this process are immune cells. They accumulate at hypoxic sites, but the kinetics, dynamics, and regulation of that trafficking are unknown. In this study, we used intravital and live cell imaging to understand how neutrophils and macrophages migrate and behave at angiogenic sites. We developed two reproducible models of angiogenesis: one by transplanting isolated and hypoxic pancreatic islets into the cremaster muscles of mice, and another by in vitro coculturing of mouse aortic rings with neutrophils...
June 5, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28583545/simultaneous-subtotal-pancreatectomy-and-streptozotocin-injection-for-diabetes-modeling-in-cynomolgus-monkeys
#11
H Park, J B Park, J H Kim, K W Lee, H S Lee, G-S Kim, D-Y Shin, S-H Oh, S-M Jin, S J Kim
BACKGROUND: In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM. METHODS: IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement...
June 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28580284/nnt-reverse-mode-of-operation-mediates-glucose-control-of-mitochondrial-nadph-and-glutathione-redox-state-in-mouse-pancreatic-%C3%AE-cells
#12
Laila R B Santos, Carole Muller, Arnaldo H de Souza, Hilton K Takahashi, Peter Spégel, Ian R Sweet, Heeyoung Chae, Hindrik Mulder, Jean-Christophe Jonas
OBJECTIVE: The glucose stimulation of insulin secretion (GSIS) by pancreatic β-cells critically depends on increased production of metabolic coupling factors, including NADPH. Nicotinamide nucleotide transhydrogenase (NNT) typically produces NADPH at the expense of NADH and ΔpH in energized mitochondria. Its spontaneous inactivation in C57BL/6J mice was previously shown to alter ATP production, Ca(2+) influx, and GSIS, thereby leading to glucose intolerance. Here, we tested the role of NNT in the glucose regulation of mitochondrial NADPH and glutathione redox state and reinvestigated its role in GSIS coupling events in mouse pancreatic islets...
June 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28575322/mutant-mice-with-calcium-sensing-receptor-casr-activation-have-hyperglycemia-that-is-rectified-by-calcilytic-therapy
#13
Valerie N Babinsky, Fadil M Hannan, Reshma D Ramracheya, Quan Zhang, M Andrew Nesbit, Alison Hugill, Liz Bentley, Tertius A Hough, Elizabeth Joynson, Michelle Stewart, Abhishek Aggarwal, Maximilian Prinz-Wohlgenannt, Caroline M Gorvin, Enikö Kallay, Sara Wells, Roger D Cox, Duncan Richards, Patrik Rorsman, Rajesh V Thakker
The calcium-sensing receptor (CaSR) is a family C G-protein-coupled receptor (GPCR) that plays a pivotal role in extracellular calcium homeostasis. The CaSR is also highly expressed in pancreatic islet α- and β-cells that secrete glucagon and insulin, respectively. To determine whether the CaSR may influence systemic glucose homeostasis, we characterized a mouse model with a germline gain-of-function CaSR mutation, Leu723Gln, referred to as Nuclear flecks (Nuf). Heterozygous- (CasrNuf/+) and homozygous-affected (CasrNuf/Nuf) mice were shown to have hypocalcemia in association with impaired glucose tolerance and insulin secretion...
June 2, 2017: Endocrinology
https://www.readbyqxmd.com/read/28562418/autologous-islet-transplantation-challenges-and-lessons
#14
Ty B Dunn, Joshua J Wilhelm, Melena D Bellin, Timothy L Pruett
PURPOSE OF REVIEW: Human islet isolation and autotransplantation [autologous islet transplant (AUTX)] is performed to prevent or ameliorate brittle diabetes after total pancreatectomy performed for benign disease. The success or failure of the transplant can be associated with a profound impact on the individual's quality of life and even survival. AUTX offers unique insights into the effects of pancreas quality, islet number, isolation technique and alternate site engraftment on transplant efficacy...
May 29, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28549828/deficiency-of-long-isoforms-of-nfe2l1-sensitizes-min6-pancreatic-%C3%AE-cells-to-arsenite-induced-cytotoxicity
#15
Qi Cui, Jingqi Fu, Yuxin Hu, Yongfang Li, Bei Yang, Lu Li, Jing Sun, Chengjie Chen, Guifan Sun, Yuanyuan Xu, Qiang Zhang, Jingbo Pi
Increasing evidence indicates that chronic inorganic arsenic exposure is associated with type 2 diabetes (T2D), a disease of growing prevalence. Pancreatic β-cells were targeted and damaged by oxidative stress induced by arsenite. We previously showed that nuclear factor erythroid 2 like 2 (Nfe2l2)-deficient pancreatic β-cells were vulnerable to cell damage induced by oxidative stressors including arsenite, due to a muted antioxidant response. Like nuclear factor erythroid 2 like 2 (NFE2L2), NFE2L1 also belongs to the cap 'n' collar (CNC) basic-region leucine zipper (bZIP) transcription factor family, and regulates antioxidant response element (ARE) related genes...
May 24, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28540469/a-3d-microfluidic-perfusion-system-made-from-glass-for-multiparametric-analysis-of-stimulus-secretioncoupling-in-pancreatic-islets
#16
Torben Schulze, Kai Mattern, Eike Früh, Lars Hecht, Ingo Rustenbeck, Andreas Dietzel
Microfluidic perfusion systems (MPS) are well suited to perform multiparametric measurements with small amounts of tissue to function as an Organ on Chip device (OOC). Such microphysiolgical characterization is particularly valuable in research on the stimulus-secretion-coupling of pancreatic islets. Pancreatic islets are fully functional competent mini-organs, which serve as fuel sensors and transduce metabolic activity into rates of hormone secretion. To enable the simultaneous measurement of fluorescence and oxygen consumption we designed a microfluidic perfusion system from borosilicate glass by 3D femtosecond laser ablation...
September 2017: Biomedical Microdevices
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
#17
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/28532102/islet-encapsulated-implantable-composite-hollow-fiber-membrane-based-device-a-bioartificial-pancreas
#18
Rohit S Teotia, Sachin Kadam, Atul Kumar Singh, Surendra Kumar Verma, Ashutosh Bahulekar, Sujata Kanetkar, Jayesh Bellare
Islets from xeno-sources and islet like clusters derived from autologus stem cells have emerged as alternatives to cadaveric pancreas used for treatment of type 1 diabetes. However, the immuno-isolation of these islets from the host immune system suffers from the issue of biocompatibility and hypoxia. To overcome the issues of immunobarrier biocompatibility, we developed a Polysulfone (Psf)/TPGS composite hollow fiber membrane (HFM) using a hollow fiber spinning pilot plant specially developed for this purpose...
August 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28516842/serotype-distribution-antimicrobial-resistance-and-prevalence-of-pilus-islets-in-pneumococci-following-the-use-of-conjugate-vaccines
#19
Mitsuyo Kawaguchiya, Noriko Urushibara, Meiji Soe Aung, Masaaki Shinagawa, Satoshi Takahashi, Nobumichi Kobayashi
PURPOSE: In Japan, the 7-valent pneumococcal vaccine (PCV7) was introduced in 2010 and, in 2013, the PCV7 was replaced with the 13-valent pneumococcal vaccine (PCV13). This study was conducted to investigate serotypes, antimicrobial resistance and prevalence of pilus islets in pneumococcal isolates from inpatients in a Japanese tertiary hospital. METHODOLOGY: From April 2011 to February 2016, 151 isolates [95 (18 children, 77 adults) and 56 (19 children, 37 adults) in the PCV7 and PCV13 periods, respectively] were collected...
May 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28508555/laminin-and-collagen-iv-inclusion-in-immunoisolating-microcapsules-reduces-cytokine-mediated-cell-death-in-human-pancreatic-islets
#20
Alberto Llacua, Bart J de Haan, Paul de Vos
Extracellular matrix (ECM) molecules have several functions in pancreatic islets including provision of mechanical support and prevention of cytotoxicity during inflammation. During islet isolation, ECM-connections are damaged and are not restored after encapsulation and transplantation. Inclusion of specific combinations of collagen type IV and laminins in immunoisolating capsules can enhance survival of pancreatic islets. Here we investigated whether ECM can also enhance survival and lower susceptibility of human islets to cytokine-mediated cytotoxicity...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
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