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https://www.readbyqxmd.com/read/29932262/human-mesenchymal-stem-cells-derived-exosomes-are-important-in-enhancing-porcine-islet-resistance-to-hypoxia
#1
Wei Nie, Xiaoqian Ma, Cejun Yang, Zeyi Chen, Pengfei Rong, Minghua Wu, Jianhui Jiang, Mengqun Tan, Shounan Yi, Wei Wang
BACKGROUND: Hypoxia-induced damage is one of the key factors associated with islet graft dysfunction. Mesenchymal stem cells (MSCs) could be used to enhance the therapeutic effect of islet transplantation due to their paracrine potential such as exosomes. In this study, we investigated whether exosomes from human umbilical cord-derived MSC-conditioned medium (hu-MSC-CM) could increase the survival and function of neonatal porcine islet cell clusters (NICCs) exposed to hypoxia. METHODS: Neonatal porcine islet cell clusters were cultured with hu-MSC-CM, with or without exosomes, and native medium RPMI-1640 (Control) under hypoxic conditions (1% O2 )...
June 22, 2018: Xenotransplantation
https://www.readbyqxmd.com/read/29929439/comparison-of-acute-gene-expression-profiles-of-islet-cells-obtained-via-laser-capture-microdissection-between-alloxan-and-streptozotocin-treated-rats
#2
Yuki Kato, Yusaku Masago, Chiaki Kondo, Erika Yogo, Mikinori Torii, Atsuko Hishikawa, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
To identify the molecular profiles of islets from alloxan (ALX)- and streptozotocin (STZ)-treated rats, a microarray-based global gene expression analysis was performed on frozen islets isolated via laser capture microdissection. At 6 weeks old, rats were injected with ALX (40 mg/kg) or STZ (50 or 100 mg/kg) and then euthanized 24 hr later. Histopathological analysis showed β-cell necrosis, macrophage infiltration, and islet atrophy. The extent of these changes was more notable in the STZ groups than in the ALX group...
January 1, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29929213/gut-microbiome-in-type-1-diabetes-a-comprehensive-review
#3
REVIEW
Peilin Zheng, Zhixia Li, Zhiguang Zhou
Type 1 diabetes (T1D) is an autoimmune disease, which is characterized by the destruction of islet β cells in the pancreas triggered by genetic and environmental factors. In past decades, extensive familial and genome-wide association studies have revealed more than 50 risk loci in the genome. However, genetic susceptibility cannot explain the increased incidence of T1D worldwide, which is very likely attributed by the growing impact of environmental factors, especially gut microbiome. Recently, the role of gut microbiome in the pathogenesis of T1D have been uncovered by the increasing evidence from both human subjects and animal models, strongly indicating that gut microbiome might be a pivotal hub of T1D-triggering factors, especially environmental factors...
June 21, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29925956/author-correction-pancreas-regeneration
#4
Qiao Zhou, Douglas A Melton
Change history: In this Insight Review, '1989' has been changed to '1998' in the sentence "This deep understanding of pancreatic development was put to the service of regenerative medicine in 1998, when human embryonic stem cells (hES cells) were successfully cultured and opened the door to developing methods of deriving pancreatic islets from hES cells66.". This error has been corrected online.
June 20, 2018: Nature
https://www.readbyqxmd.com/read/29925930/elevated-t-cell-levels-in-peripheral-blood-predict-poor-clinical-response-following-rituximab-treatment-in-new-onset-type-1-diabetes
#5
Peter S Linsley, Carla J Greenbaum, Mario Rosasco, Scott Presnell, Kevan C Herold, Matthew J Dufort
Biologic treatment of type 1 diabetes (T1D) with agents including anti-CD3 (otelixizumab and teplizumab), anti-CD20 (rituximab), LFA3Ig (alafacept), and CTLA4Ig (abatacept) results in transient stabilization of insulin C-peptide, a surrogate for endogenous insulin secretion. With the goal of inducing more robust immune tolerance, we used systems biology approaches to elucidate mechanisms associated with C-peptide stabilization in clinical trial blood samples from new-onset T1D subjects treated with the B cell-depleting drug, rituximab...
June 21, 2018: Genes and Immunity
https://www.readbyqxmd.com/read/29925744/effect-of-lipoprotein-associated-phospholipase-a2-inhibitor-on-insulin-resistance-in-streptozotocin-induced-diabetic-pregnant-rats
#6
Guo-Hua Wang, Jun Jin, Li-Zhou Sun
This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining...
June 21, 2018: Endocrine Journal
https://www.readbyqxmd.com/read/29925687/androgen-excess-in-pancreatic-%C3%AE-cells-and-neurons-predisposes-female-mice-to-type-2-diabetes
#7
Guadalupe Navarro, Camille Allard, Jamie J Morford, Weiwei Xu, Suhuan Liu, Adrien Jr Molinas, Sierra M Butcher, Nicholas Hf Fine, Manuel Blandino-Rosano, Venkata N Sure, Sangho Yu, Rui Zhang, Heike Münzberg, David A Jacobson, Prasad V Katakam, David J Hodson, Ernesto Bernal-Mizrachi, Andrea Zsombok, Franck Mauvais-Jarvis
Androgen excess predisposes women to type 2 diabetes (T2D), but the mechanism of this is poorly understood. We report that female mice fed a Western diet and exposed to chronic androgen excess using dihydrotestosterone (DHT) exhibit hyperinsulinemia and insulin resistance associated with secondary pancreatic β cell failure, leading to hyperglycemia. These abnormalities are not observed in mice lacking the androgen receptor (AR) in β cells and partially in neurons of the mediobasal hypothalamus (MBH) as well as in mice lacking AR selectively in neurons...
June 21, 2018: JCI Insight
https://www.readbyqxmd.com/read/29921789/fatty-acid-stimulated-insulin-secretion-vs-lipotoxicity
#8
REVIEW
Petr Ježek, Martin Jabůrek, Blanka Holendová, Lydie Plecitá-Hlavatá
Fatty acid (FA)-stimulated insulin secretion (FASIS) is reviewed here in contrast to type 2 diabetes etiology, resulting from FA overload, oxidative stress, intermediate hyperinsulinemia, and inflammation, all converging into insulin resistance. Focusing on pancreatic islet β-cells, we compare the physiological FA roles with the pathological ones. Considering FAs not as mere amplifiers of glucose-stimulated insulin secretion (GSIS), but as parallel insulin granule exocytosis inductors, partly independent of the KATP channel closure, we describe the FA initiating roles in the prediabetic state that is induced by retardations in the glycerol-3-phosphate (glucose)-promoted glycerol/FA cycle and by the impaired GPR40/FFA1 (free FA1) receptor pathway, specifically in its amplification by the redox-activated mitochondrial phospholipase, iPLA2γ...
June 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29920277/postnatal-exocrine-pancreas-growth-by-cellular-hypertrophy-correlates-with-a-shorter-lifespan-in-mammals
#9
Shira Anzi, Miri Stolovich-Rain, Agnes Klochendler, Ori Fridlich, Aharon Helman, Avital Paz-Sonnenfeld, Nili Avni-Magen, Elizabeth Kaufman, Miriam B Ginzberg, Daniel Snider, Saikat Ray, Michael Brecht, Melissa M Holmes, Karen Meir, Aaron Avivi, Imad Shams, Asaf Berkowitz, A M James Shapiro, Benjamin Glaser, Shmuel Ben-Sasson, Ran Kafri, Yuval Dor
Developmental processes in different mammals are thought to share fundamental cellular mechanisms. We report a dramatic increase in cell size during postnatal pancreas development in rodents, accounting for much of the increase in organ size after birth. Hypertrophy of pancreatic acinar cells involves both higher ploidy and increased biosynthesis per genome copy; is maximal adjacent to islets, suggesting endocrine to exocrine communication; and is partly driven by weaning-related processes. In contrast to the situation in rodents, pancreas cell size in humans remains stable postnatally, indicating organ growth by pure hyperplasia...
June 18, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29916530/mir%C3%A2-6835%C3%A2-3p-regulates-the-function-of-pancreatic-islet-cells-by-modulating-the-expression-of-adipor1
#10
Huimin Wang, Lei Jiang, Zhenfu Li, Wei Wang, Chuanji Hao
Effective drugs and strategies for treating type 2 diabetes mellitus (2‑DM) are urgently required. The aim of the present study was to elucidate the mechanism underlying microRNA (miR)‑6835‑3p regulation of adiponectin receptor 1 (AdipoR1) expression and the miR‑6835‑3p/AdipoR1 signaling pathway in pancreatic islet cells. In addition, the potential anti‑diabetes effect of miR‑6835‑3p on insulin secretion was investigated. Luciferase activity analysis was performed to evaluate how miR‑6835‑3p targets the 3'‑untranslated region of AdipoR1...
June 15, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29916364/a-new-mode-of-pancreatic-islet-innervation-revealed-by-live-imaging-in-zebrafish
#11
Yu Hsuan Carol Yang, Koichi Kawakami, Didier Yr Stainier
Pancreatic islets are innervated by autonomic and sensory nerves that influence their function. Analyzing the innervation process should provide insight into the nerve-endocrine interactions and their roles in development and disease. Here, using in vivo time-lapse imaging and genetic analyses in zebrafish, we determined the events leading to islet innervation. Comparable neural density in the absence of vasculature indicates that it is dispensable for early pancreatic innervation. Neural crest cells are in close contact with endocrine cells early in development...
June 19, 2018: ELife
https://www.readbyqxmd.com/read/29915142/impaired-%C3%AE-cell-glucokinase-as-an-underlying-mechanism-in-diet-induced-diabetes
#12
Brian Lu, Kiran Kurmi, Miguel Munoz-Gomez, Egon J Jacobus Ambuludi, Jason M Tonne, Kuntol Rakshit, Taro Hitosugi, Yogish C Kudva, Aleksey V Matveyenko, Yasuhiro Ikeda
High-fat diet (HFD)-fed mouse models have been widely used to study early type 2 diabetes. Decreased β-cell glucokinase (GCK) expression has been observed in HFD-induced diabetes. However, owing to its crucial roles in glucose metabolism in the liver and in islet β-cells, the contribution of decreased GCK expression to the development of HFD-induced diabetes is unclear. Here, we employed a β-cell-targeted gene transfer vector and determined the impact of β-cell-specific increase in GCK expression on β-cell function and glucose handling in vitro and in vivo Overexpression of GCK enhanced glycolytic flux, ATP-sensitive potassium channel activation and membrane depolarization, and increased proliferation in Min6 cells...
June 13, 2018: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29914854/pancreatic-deletion-of-the-interleukin-1-receptor-disrupts-whole-body-glucose-homeostasis-and-promotes-islet-%C3%AE-cell-de-differentiation
#13
Susan J Burke, Heidi M Batdorf, David H Burk, Thomas M Martin, Tamra Mendoza, Krisztian Stadler, Wateen Alami, Michael D Karlstad, Matthew J Robson, Randy D Blakely, Randall L Mynatt, J Jason Collier
OBJECTIVE: Pancreatic tissue, and islets in particular, are enriched in expression of the interleukin-1 receptor type I (IL-1R). Because of this enrichment, islet β-cells are exquisitely sensitive to the IL-1R ligands IL-1α and IL-1β, suggesting that signaling through this pathway regulates health and function of islet β-cells. METHODS: Herein, we report a targeted deletion of IL-1R in pancreatic tissue (IL-1RPdx1-/- ) in C57BL/6J mice and in db/db mice on the C57 genetic background...
June 6, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29913560/maternal-folic-acid-supplementation-with-vitamin-b-12-deficiency-during-pregnancy-and-lactation-affects-the-metabolic-health-of-adult-female-offspring-but-is-dependent-on-offspring-diet
#14
Amanda M Henderson, Daven C Tai, Rika E Aleliunas, Abeer M Aljaadi, Melissa B Glier, Eric E Xu, Joshua W Miller, C Bruce Verchere, Tim J Green, Angela M Devlin
Epidemiologic studies have reported relationships between maternal high folate and/or low B12 status during pregnancy and greater adiposity and insulin resistance in children. The goal of this study was to determine the effects of maternal folic acid supplementation (10 mg/kg diet), with (50 μg/kg diet) and without B12 , on adult, female offspring adiposity and glucose homeostasis. Female C57BL/6J mice were fed 1 of 3 diets from weaning and throughout breeding, pregnancy, and lactation: control (2 mg/kg diet folic acid, 50 μg/kg diet B12 ), supplemental folic acid with no B12 (SFA-B12 ), or supplemental folic acid with adequate B12 (SFA+B12 )...
April 17, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29912854/spexin-modulates-functions-of-rat-endocrine-pancreatic-cells
#15
Maciej Sassek, Pawel A Kolodziejski, Mathias Z Strowski, Leszek Nogowski, Krzysztof W Nowak, Pawel Mackowiak
OBJECTIVES: Spexin is a peptide whose action is poorly understood but which is expressed in many tissues. This encouraged us to investigate the potential role of spexin in the regulation of pancreatic secretion. METHODS: Cells/islets were incubated with different concentrations of glucose and spexin to measure insulin secretion. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and BrdU (5-bromo-2'-deoxyuridine) tests were performed to assess the viability and proliferation of pancreatic islets after spexin treatment...
June 16, 2018: Pancreas
https://www.readbyqxmd.com/read/29910119/secretagogin-protects-pdx1-from-proteasomal-degradation-to-control-a-transcriptional-program-required-for-%C3%AE-cell-specification
#16
Katarzyna Malenczyk, Edit Szodorai, Robert Schnell, Gert Lubec, Gábor Szabó, Tomas Hökfelt, Tibor Harkany
OBJECTIVE: Specification of endocrine cell lineages in the developing pancreas relies on extrinsic signals from non-pancreatic tissues, which initiate a cell-autonomous sequence of transcription factor activation and repression switches. The steps in this pathway share reliance on activity-dependent Ca2+ signals. However, the mechanisms by which phasic Ca2+ surges become converted into a dynamic, cell-state-specific and physiologically meaningful code made up by transcription factors constellations remain essentially unknown...
June 5, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29909496/transplantation-of-macroencapsulated-insulin-producing-cells
#17
REVIEW
Albert J Hwa, Gordon C Weir
PURPOSE OF REVIEW: There is considerable interest in using macroencapsulation devices as a delivery strategy for transplanting insulin-producing cells. This review aims to summarize recent advances, to highlight remaining challenges, and to provide recommendations for the field. RECENT FINDINGS: A variety of new device designs have been reported to improve biocompatibility and to provide protection for islet/beta cells from immune destruction while allowing continuous secretion of insulin...
June 16, 2018: Current Diabetes Reports
https://www.readbyqxmd.com/read/29909240/tissue-specific-expression-and-circulating-concentrations-of-nesfatin-1-in-domestic-animals
#18
K A Morton, L Hargreaves, S Mortazavi, L P Weber, A M Blanco, S Unniappan
Nesfatin-1 is a naturally occurring 82-amino acid protein encoded in the precursor nucleobindin-2 (NUCB2) and has been implicated in multiple physiological functions, including food intake and blood glucose regulation. This study aimed to characterize nesfatin-1 in domestic species, especially cats (Felis catus), dogs (Canis lupus familiaris), and pigs (Sus scrofa). Our in silico analysis demonstrated that the NUCB2/nesfatin-1 amino acid sequence, especially the bioactive core region of the peptide, is very highly conserved (more than 90% identity) in domestic animals...
May 9, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29909196/bioelectronic-organ-based-sensor-for-microfluidic-real-time-analysis-of-the-demand-in-insulin
#19
R Perrier, A Pirog, M Jaffredo, J Gaitan, B Catargi, S Renaud, M Raoux, J Lang
On-line and real-time analysis of micro-organ activity permits to use the endogenous analytical power of cellular signal transduction algorithms as biosensors. We have developed here such a sensor using only a few pancreatic endocrine islets and the avoidance of transgenes or chemical probes reduces bias and procures general usage. Nutrient and hormone-induced changes in islet ion fluxes through channels provide the first integrative read-out of micro-organ activity. Using extracellular electrodes we captured this read-out non-invasively as slow potentials which reflect glucose concentration-dependent (3-15 mM) micro-organ activation and coupling...
June 8, 2018: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/29908844/tissue-associated-self-antigens-containing-exosomes-role-in-allograft-rejection
#20
Monal Sharma, Ranjithkumar Ravichandran, Sandhya Bansal, Ross M Bremner, Michael A Smith, T Mohanakumar
Exosomes are extracellular vesicles that express self-antigens (SAgs) and donor human leukocyte antigens. Tissue-specific exosomes can be detected in the circulation following lung, heart, kidney and islet cell transplantations. We collected serum samples from patients who had undergone lung (n = 30), heart (n = 8), or kidney (n = 15) transplantations to isolate circulating exosomes. Exosome purity was analyzed by Western blot, using CD9 exosome-specific markers. Tissue-associated lung SAgs, collagen V (Col-V) and K-alpha 1 tubulin (Kα1T), heart SAgs, myosin and vimentin, and kidney SAgs, fibronectin and collagen IV (Col-IV), were identified using western blot...
June 15, 2018: Human Immunology
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