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https://www.readbyqxmd.com/read/28822218/locally-produced-xenin-and-the-neurotensinergic-system-in-pancreatic-islet-function-and-%C3%AE-cell-survival
#1
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Victor A Gault, Peter R Flatt, Nigel Irwin
Modulation of neuropeptide receptors is important for pancreatic β-cell function. Here, islet distribution and effects of the neurotensin (NT) receptor modulators, xenin and NT, was examined. Xenin, but not NT, significantly improved glucose disposal and insulin secretion, in mice. However, both peptides stimulated insulin secretion from rodent β-cells at 5.6 mM glucose, with xenin having similar insulinotropic actions at 16.7 mM glucose. In contrast, NT inhibited glucose-induced insulin secretion. Similar observations were made in human 1...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28821639/amyloid-induced-%C3%AE-cell-dysfunction-and-islet-inflammation-are-ameliorated-by-4-phenylbutyrate-pba-treatment
#2
Joel Montane, Sara de Pablo, Carlos Castaño, Júlia Rodríguez-Comas, Lisa Cadavez, Mercè Obach, Montse Visa, Gema Alcarraz-Vizán, Melchor Sanchez-Martinez, Alfons Nonell-Canals, Marcelina Parrizas, Joan-Marc Servitja, Anna Novials
Human islet amyloid polypeptide (hIAPP) aggregation is associated with β-cell dysfunction and death in type 2 diabetes (T2D). we aimed to determine whether in vivo treatment with chemical chaperone 4-phenylbutyrate (PBA) ameliorates hIAPP-induced β-cell dysfunction and islet amyloid formation. Oral administration of PBA in transgenic (Tg) mice expressing hIAPP in pancreatic β cells (hIAPP Tg) counteracted impaired glucose homeostasis and restored glucose-stimulated insulin secretion. Moreover, PBA treatment almost completely prevented the transcriptomic alterations observed in hIAPP Tg islets, including the induction of genes related to inflammation...
August 15, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28819632/detection-of-islet-cell-immune-reactivity-with-low-glycemic-index-foods-is-this-a-concern-for-type-1-diabetes
#3
Datis Kharrazian, Martha Herbert, Aristo Vojdani
Dietary management of autoimmune diabetes includes low glycemic foods classified from the glycemic index, but it does not consider the role that immunoreactive foods may play with the immunological etiology of the disease. We measured the reactivity of either monoclonal or polyclonal affinity-purified antibodies to insulin, insulin receptor alpha, insulin receptor beta, zinc transporter 8 (ZnT8), tyrosine phosphatase-based islet antigen 2 (IA2), and glutamic acid decarboxylase (GAD) 65 and 67 against 204 dietary proteins that are commonly consumed...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28813430/reprogramming-human-gallbladder-cells-into-insulin-producing-%C3%AE-like-cells
#4
Feorillo Galivo, Eric Benedetti, Yuhan Wang, Carl Pelz, Jonathan Schug, Klaus H Kaestner, Markus Grompe
The gallbladder and cystic duct (GBCs) are parts of the extrahepatic biliary tree and share a common developmental origin with the ventral pancreas. Here, we report on the very first genetic reprogramming of patient-derived human GBCs to β-like cells for potential autologous cell replacement therapy for type 1 diabetes. We developed a robust method for large-scale expansion of human GBCs ex vivo. GBCs were reprogrammed into insulin-producing pancreatic β-like cells by a combined adenoviral-mediated expression of hallmark pancreatic endocrine transcription factors PDX1, MAFA, NEUROG3, and PAX6 and differentiation culture in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28812213/heterogeneity-in-the-beta-cell-population-a-guided-search-into-its-significance-in-pancreas-and-in-implants
#5
REVIEW
Daniel Pipeleers, Ines De Mesmaeker, Thomas Robert, Freya Van Hulle
PURPOSE OF REVIEW: Intercellular differences in function have since long been noticed in the pancreatic beta-cell population. Heterogeneity in cellular glucose responsiveness is considered of physiological and pathological relevance. The present review updates evidence for the physiologic significance of beta-cell heterogeneity in the pancreas. It also briefly discusses what this role would imply for beta-cell implants in diabetes. RECENT FINDINGS: Over the past 3 years, functionally different beta cells have been related to mechanisms that may underlie their heterogeneity in the pancreas, such as the stage in their life cycle and the degree of their clustering to islets with varying vascularization...
August 15, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28811318/the-%C3%AE-cell-assassin-iapp-cytotoxicity
#6
Daniel Raleigh, Xiaoxue Zhang, Benoit Hastoy, Anne Clark
Islet amyloid polypeptide (IAPP) forms cytotoxic oligomers and amyloid fibrils in islets in Type 2 diabetes (T2DM). The causal factors for amyloid formation are largely unknown. Mechanisms of molecular folding and assembly of human IAPP (hIAPP) into β-sheets, oligomers and fibrils have been assessed by detailed biophysical studies of hIAPP and non-fibrillogenic, rodent IAPP (rIAPP); cytotoxicity is associated with the early phases (oligomers/multimers) of fibrillogenesis. Interaction with synthetic membranes promotes β-sheet assembly possibly via a transient α-helical molecular conformation...
August 15, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28808402/role-of-adiantum-philippense-l-on-glucose-uptake-in-isolated-pancreatic-cells-and-inhibition-of-adipocyte-differentiation-in-3t3-l1-cell-line
#7
Tania Paul, Kishori G Apte, Pradeep B Parab, Biswadeep Das
BACKGROUND: Adiantum philippense (AP) is a pteridophyte that shows antihyperglycemic activity in vivo diabetic model, but the mechanism of action is unknown. OBJECTIVE: AP was found to play a pivotal role in minimizing the high blood glucose in alloxan-induced diabetic rats. Simultaneously, it was observed that it could maintain the normal lipid profile even in diabetic condition. To investigate its insulin-like activity along with its inhibitory role on adipocyte differentiation became the objective of our present study...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808140/amyloid-%C3%AE-and-islet-amyloid-pathologies-link-alzheimer-disease-and-type-2-diabetes-in-a-transgenic-model
#8
Nadeeja Wijesekara, Rosemary Ahrens, Miheer Sabale, Ling Wu, Kathy Ha, Giuseppe Verdile, Paul E Fraser
Alzheimer's disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-β (Aβ) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases. A novel double transgenic mouse model combining T2D and AD was generated and characterized. AD-related amyloid transgenic mice coexpressing hIAPP displayed peripheral insulin resistance, hyperglycemia, and glucose intolerance...
August 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28808079/the-impact-of-iugr-on-pancreatic-islet-development-and-%C3%AE-cell-function
#9
Brit H Boehmer, Sean W Limesand, Paul J Rozance
Placental insufficiency is a primary cause of intrauterine growth restriction (IUGR). IUGR increases the risk of developing type 2 diabetes mellitus (T2DM) throughout life, which indicates that insults from placental insufficiency impair β-cell development during the perinatal period because β-cells have a central role in the regulation of glucose tolerance. The severely IUGR fetal pancreas is characterized by smaller islets, less β-cells, and lower insulin secretion. Because of the important associations among impaired islet growth, β-cell dysfunction, impaired fetal growth, and the propensity for T2DM, significant progress has been made in understanding the pathophysiology of IUGR and programing events in the fetal endocrine pancreas...
August 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28807051/mesenchymal-stromal-cells-ameliorate-oxidative-stress-induced-islet-endothelium-apoptosis-and-functional-impairment-via-wnt4-%C3%AE-catenin-signaling
#10
Lingshu Wang, Li Qing, He Liu, Na Liu, Jingting Qiao, Chen Cui, Tianyi He, Ruxing Zhao, Fuqiang Liu, Fei Yan, Chuan Wang, Kai Liang, Xinghong Guo, Ying H Shen, Xinguo Hou, Li Chen
BACKGROUND: Islet dysfunction and destruction are the common cause for both type 1 and type 2 diabetes mellitus (T2DM). The islets of Langerhans are highly vascularized miniorgans, and preserving the structural integrity and full function of the microvascular endothelium is vital for protecting the islets from the infiltration of immune cells and secondary inflammatory attack. Mesenchymal stromal cell (MSC)-based therapies have been proven to promote angiogenesis of the islets; however, the underlying mechanism for the protective role of MSCs in the islet endothelium is still vague...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28805970/a-novel-free-fatty-acid-receptor-1-gpr40-ffar1-agonist-mr1704-enhances-glucose-dependent-insulin-secretion-and-improves-glucose-homeostasis-in-rats
#11
Naoto Tsuda, Atsuko Kawaji, Toshihiro Sato, Mitsuhiro Takagi, Chika Higashi, Yutaka Kato, Kumiko Ogawa, Hiroyasu Naba, Munetaka Ohkouchi, Masaki Nakamura, Yoshitaka Hosaka, Junichi Sakaki
Activation of G protein-coupled receptor 40/Free fatty acid receptor 1 (GPR40/FFAR1), which is highly expressed in pancreatic β cells, is considered an important pharmacologic target for the treatment of type 2 diabetes mellitus. The aim of this study was to determine the effect of MR1704, a novel GPR40/FFAR1 agonist, on glucose homeostasis in rats. MR1704 is a highly potent and selective, orally bioavailable agonist with similar in vitro potencies among humans, mice, and rats. Treatment of rat islets with MR1704 increased glucose-dependent insulin secretion...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28803916/mitigating-ischemic-injury-of-stem-cell-derived-insulin-producing-cells-after-transplant
#12
Gaetano Faleo, Holger A Russ, Steven Wisel, Audrey V Parent, Vinh Nguyen, Gopika G Nair, Jonathan E Freise, Karina E Villanueva, Gregory L Szot, Matthias Hebrok, Qizhi Tang
The advent of large-scale in vitro differentiation of human stem cell-derived insulin-producing cells (SCIPC) has brought us closer to treating diabetes using stem cell technology. However, decades of experiences from islet transplantation show that ischemia-induced islet cell death after transplant severely limits the efficacy of the therapy. It is unclear to what extent human SCIPC are susceptible to ischemia. In this study, we show that more than half of SCIPC die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPC in vitro...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28802201/biomimetic-surfaces-supporting-dissociated-pancreatic-islet-cultures
#13
Parker L Andersen, Patrick Vermette
This study describes a method to screen biomimetic surfaces based on intracellular insulin content of either fully or partly dissociated primary endocrine islet tissue. It is challenging to maintain endocrine pancreatic islets and more so, dissociated ones. Physiological activity of isolated islet cells in vitro declines due to loss of cell-to-cell and cell-to-extracellular matrix interactions. An in vitro model was developed to evaluate specific extracellular binding components potentially affecting islet biology, with the intention to identify in vivo-like peptides promoting survival and function...
July 25, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28801867/regulation-of-the-aggregation-behavior-of-human-islet-amyloid-polypeptide-fragment-by-titanocene-complexes
#14
Weihong Du, Gehui Gong, Wenji Wang, Jufei Xu
The aggregation of human islet amyloid polypeptide (hIAPP) is associated with type II diabetes. The misfolding of hIAPP induces amyloid deposition and causes β-cell dysfunction. Metal complexes are potential metallodrugs that may reverse the aggregation of amyloid peptides. hIAPP19-37 is a crucial fragment of the full-length hIAPP1-37 and contains typical aromatic residues and a core hydrophobic region. In this work, we studied the effects of titanocene complexes titanocene dichloride (1), titanocene salicylic acid complex (2), and titanocene methionine complex (3) on the aggregation behavior of hIAPP19-37...
August 11, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28801684/structural-properties-of-human-iapp-dimer-in-membrane-environment-studied-by-all-atom-molecular-dynamics-simulations
#15
Na Liu, Mojie Duan, Minghui Yang
The aggregation of human islet amyloid polypeptide (hIAPP) can damage the membrane of the β-cells in the pancreatic islets and induce type 2 diabetes (T2D). Growing evidences indicated that the major toxic species are small oligomers of IAPP. Due to the fast aggregation nature, it is hard to characterize the structures of IAPP oligomers by experiments, especially in the complex membrane environment. On the other side, molecular dynamics simulation can provide atomic details of the structure and dynamics of the aggregation of IAPP...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801594/deficiency-in-catechol-o-methyltransferase-is-linked-to-a-disruption-of-glucose-homeostasis-in-mice
#16
Megumi Kanasaki, Swayam Prakash Srivastava, Fan Yang, Ling Xu, Sumiyo Kudoh, Munehiro Kitada, Norikazu Ueki, Hyoh Kim, Jinpeng Li, Satoru Takeda, Keizo Kanasaki, Daisuke Koya
2-methoxyestradiol (2-ME), an estrogen metabolite generated via catechol-o-methyltransferase (COMT), is multifunctional methoxy-catechol. Here, we report that COMT deficiency leads to glucose intolerance and 2-ME rescues COMT-deficient-associated metabolic defects. Liver COMT protein was suppressed in high fat diet (HFD)-fed or in pregnant mice. COMT suppression, by Ro41-0960 or siRNA, in HFD fed mice or in pregnant mice exacerbated glucose intolerance; 2-ME intervention ameliorated these defects. 2-ME effects on glucose tolerance were associated with AMPK phosphorylation in the liver and in islet cells...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801559/differential-effects-of-linagliptin-on-the-function-of-human-islets-isolated-from-non-diabetic-and-diabetic-donors
#17
Yanqing Zhang, Meifen Wu, Wynn Htun, Emily W Dong, Franck Mauvais-Jarvis, Vivian A Fonseca, Hongju Wu
Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated islets from normal subjects. Since β cell dysfunction occurs during diabetes development, it was not clear how human islets of T2D patients would respond to linagliptin treatment. Therefore, in this study we employed human islets isolated from donors with and without T2D and evaluated how they responded to linagliptin treatment...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801292/-oxidized-low-density-lipoprotein-modulates-differentiation-of-murine-memory-cd8-t-cell-subpopulations
#18
Hua Zheng, Ze-Hang Lin, Yan-Mei Zhang, Chen-Fei Zhou, Xuan Liu, Sha Wu
OBJECTIVE: To investigate effect of oxidized low-density lipoprotein (ox-LDL) on memory CD8(+) T cell subpopulation differentiation in mice with autoimmune diabetes. METHODS: Cultured splenic CD8(+) T cells from pre-diabetic NOD mice isolated with magnetic beads were treated with 30 µg/mL ox-LDL and 10 U/mL interleukin-2 (IL-2) for 24 h and the control cells were treated with IL-2 only. Flow cytometry was used to determine the percentage of splenic CD8(+)IFN-γ(+) T cells, expressions of CD8, CD44 and CD62L on the T cells, and the activation of T cell factor-1 (TCF-1) and STAT-3...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28800882/salvianolic-acid-b-inhibits-intermittent-high-glucose-induced-ins-1-cell-apoptosis-through-regulation-of-bcl-2-proteins-and-mitochondrial-membrane-potential
#19
Shanjun Tao, Younan Ren, Haowen Zheng, Mengqiu Zhao, Xu Zhang, Yuanmei Zhu, Jieren Yang, Shuguo Zheng
Blood glucose fluctuations, also referred to as intermittent high glucose, have been validated to be more harmful than sustained high glucose in exacerbating pancreatic dysfunction by inducing β cell apoptosis. Salvianolic acid B (Sal B), an aqueous component of Salvia miltiorrhiza, has been proved beneficial to pancreatic islet function in diabetes, but the underlying mechanisms remain to be elucidated. The present study investigated the protective effect of Sal B on INS-1 cells exposed to intermittent high glucose and the possible mechanisms implicated...
August 8, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28800453/discovery-of-cycloalkyl-fused-n-thiazol-2-yl-benzamides-as-tissue-non-specific-glucokinase-activators-design-synthesis-and-biological-evaluation
#20
Zhengyu Wang, Xiaofan Shi, Huan Zhang, Liang Yu, Yanhua Cheng, Hefeng Zhang, Huibin Zhang, Jinpei Zhou, Jing Chen, Xu Shen, Wenhu Duan
Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, we investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators, which led to the identification of compound 72 that showed a good balance between in vitro potency and enzyme kinetic parameters, and protected β-cells from streptozotocin-induced apoptosis...
July 25, 2017: European Journal of Medicinal Chemistry
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