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Pancreatic beta cells

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https://www.readbyqxmd.com/read/29050300/tfcp2-activates-beta-catenin-tcf-signaling-in-the-progression-of-pancreatic-cancer
#1
Dai Yuedi, Cai Yuankun, Zhao Jiaying, Liu Han, Wang Yueqi, Liu Houbao, Zhang Dexiang
Aberrant activation of beta-catenin/TCF (T-cell factor) signaling is frequently observed in the pancreatic cancer. However, the regulation of nuclear beta-catenin/TCF transcription machinery remains largely unknown. In this study, TFCP2 (transcriptional factor CP2) expression in pancreatic cancer was detected by qPCR, immunohistochemistry and western blot. Western blot, colony formation assay, migration and invasion experiment were performed to investigate the effects of TFCP2 on the growth and migration of pancreatic cancer cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29044608/nutrient-sensing-in-pancreatic-islets-lessons-from-congenital-hyperinsulinism-and-monogenic-diabetes
#2
REVIEW
Ming Lu, Changhong Li
Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM))...
October 16, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29040320/circulating-microrna-375-as-biomarker-of-pancreatic-beta-cell-death-and-protection-of-beta-cell-mass-by-cytoprotective-compounds
#3
Imane Song, Sarah Roels, Geert A Martens, Luc Bouwens
OBJECTIVE: Previous studies demonstrated that circulating microRNA-375 (miR-375) is a suitable plasma biomarker for real-time detection of beta cell death. The present study evaluated the use of this biomarker to assess the beta cytoprotective effect of phenylpropenoic acid glucoside (PPAG), which was previously demonstrated to protect beta cells against various types of injury, and of exendin-4, which is an established antidiabetic drug. METHODS: PPAG or exendin-4 were administered in mice treated with streptozotocin (STZ) to acutely induce beta cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29038309/deletion-of-protein-kinase-d1-in-pancreatic-beta-cells-impairs-insulin-secretion-in-high-fat-fed-mice
#4
Valérie Bergeron, Julien Ghislain, Kevin Vivot, Natalia Tamarina, Louis H Philipson, Jens Fielitz, Vincent Poitout
Beta-cell adaptation to insulin resistance is necessary to maintain glucose homeostasis in obesity. Failure of this mechanism is a hallmark of type 2 diabetes (T2D). Hence, factors controlling functional beta-cell compensation are potentially important targets for the treatment of T2D. Protein kinase D1 (PKD1) integrates diverse signals in the beta cell and plays a critical role in the control of insulin secretion. However, the role of beta-cell PKD1 in glucose homeostasis in vivo is essentially unknown. Using beta-cell specific, inducible PKD1 knock-out mice (βPKD1KO), we examined the role of beta-cell PKD1 under basal conditions and during high-fat feeding...
October 16, 2017: Diabetes
https://www.readbyqxmd.com/read/29037070/melatonin-promotes-self-renewal-of-nestin-positive-pancreatic-stem-cells-through-activation-of-the-mt2-erk-smad-nestin-axis
#5
Chunyu Bai, Yuhua Gao, Xiangyang Zhang, Wancai Yang, Weijun Guan
Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promotion of self-renewal in pancreatic stem cells remain unknown. In this study, we incubated murine pancreatic stem cells (PSCs) with various concentrations of melatonin (0.01, 0.1, 1, 10 or 100 μM) to screen for the optimum culture medium for increasing cell proliferation. We found that 10 μM melatonin can significantly increase proliferation and enhance expression of a stem cell marker, nestin, in PSCs via melatonin receptor 2 (MT2)...
October 16, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29031718/g%C3%AE-s-regulates-glucagon-like-peptide-1-receptor-mediated-cyclic-amp-generation-at%C3%A2-rab5-endosomal-compartment
#6
Shravan Babu Girada, Ramya S Kuna, Shilpak Bele, Zhimeng Zhu, N R Chakravarthi, Richard D DiMarchi, Prasenjit Mitra
OBJECTIVE: Upon activation, G protein coupled receptors (GPCRs) associate with heterotrimeric G proteins at the plasma membrane to initiate second messenger signaling. Subsequently, the activated receptor experiences desensitization, internalization, and recycling back to the plasma membrane, or it undergoes lysosomal degradation. Recent reports highlight specific cases of persistent cyclic AMP generation by internalized GPCRs, although the functional significance and mechanistic details remain to be defined...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29030662/oral-histone-deacetylase-inhibitor-synergises-with-t-cell-targeted-immunotherapy-to-preserve-beta-cell-metabolic-function-and-induce-stable-remission-of-new-onset-autoimmune-diabetes-in-nod-mice
#7
Alix Besançon, Tania Goncalves, Fabrice Valette, Mattias S Dahllöf, Thomas Mandrup-Poulsen, Lucienne Chatenoud, Sylvaine You
AIM/HYPOTHESIS: Combination therapy targeting the major actors involved in the immune-mediated destruction of pancreatic beta cells appears to be an indispensable approach to treat type 1 diabetes effectively. We hypothesised that the combination of an orally active pan-histone deacetylase inhibitor (HDACi: givinostat) with subtherapeutic doses of CD3 antibodies may provide ideal synergy to treat ongoing autoimmunity. METHODS: NOD mice transgenic for the human CD3ε (also known as CD3E) chain (NOD-huCD3ε) were treated for recent-onset diabetes with oral givinostat, subtherapeutic doses of humanised CD3 antibodies (otelixizumab, 50 μg/day, 5 days, i...
October 13, 2017: Diabetologia
https://www.readbyqxmd.com/read/29029784/regulation-of-insulin-exocytosis-by-calcium-dependent-protein-kinase-c-in-beta-cells
#8
REVIEW
Adam J Trexler, Justin W Taraska
The control of insulin release from pancreatic beta cells helps ensure proper blood glucose level, which is critical for human health. Protein kinase C has been shown to be one key control mechanism for this process. After glucose stimulation, calcium influx into beta cells triggers exocytosis of insulin-containing dense-core granules and activates protein kinase C via calcium-dependent phospholipase C-mediated generation of diacylglycerol. Activated protein kinase C potentiates insulin release by enhancing the calcium sensitivity of exocytosis, likely by affecting two main pathways that could be linked: (1) the reorganization of the cortical actin network, and (2) the direct phosphorylation of critical exocytotic proteins such as munc18, SNAP25, and synaptotagmin...
November 2017: Cell Calcium
https://www.readbyqxmd.com/read/29029423/disc1-overexpression-promotes-non-small-cell-lung-cancer-cell-proliferation
#9
Shuo Wang, Ying-Ying Chen, Yu-Peng Li, Jun Gu, Shu-Dong Gu, Hai Shi, Xue-Song Li, Xiao-Ning Lu, Xiang Li, Shuang-Long Zhang, Kang-Jun Yu, Kun Liu, Li-Li Ji
Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1) activates Wnt/β-catenin signaling by inhibiting glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and may promote neural progenitor cell and pancreatic β-cell proliferation. The present study found that DISC1 promotes non-small cell lung cancer (NSCLC) cell growth. Western blotting and immunohistochemistry analyses showed that DISC1 was highly expressed in NSCLC cell lines and patient tissues. DISC1 expression was negatively associated with phosphorylated (p-) GSK3β, but positively correlated with a more invasive tumor phenotype and predicted poor NSCLC patient prognosis...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028203/an-information-theoretical-analysis-of-human-insulin-glucose-system-towards-the-internet-of-bio-nano-things
#10
Naveed A Abbasi, Ozgur B Akan
Molecular communication is an important tool to understand biological communications with many promising applications in Internet of Bio-Nano Things (IoBNT). The insulinglucose system is of key significance among the major intrabody nanonetworks since it fulfills metabolic requirements of the body. Study of biological networks from information and communication theoretical (ICT) perspective is necessary for their introduction in the IoBNT framework. Therefore, the objective of this work is to provide and analyze for the first time in literature, a simple molecular communication model of the human insulin-glucose system from ICT perspective...
October 11, 2017: IEEE Transactions on Nanobioscience
https://www.readbyqxmd.com/read/29025046/decreased-insulin-secretion-in-pregnant-rats-fed-a-low-protein-diet
#11
Haijun Gao, Eric Ho, Meena Balakrishnan, Vijay Yechoor, Chandra Yallampalli
Low protein (LP) diet during pregnancy leads to reduced plasma insulin levels in rodents, but the underlying mechanisms remain unclear. Glucose is the primary insulin secretagogue and enhanced glucose stimulated insulin secretion (GSIS) in beta cells contributes to compensation for insulin resistance and maintenance of glucose homeostasis during pregnancy. In this study we hypothesized that plasma insulin levels in pregnant rats fed LP diet is reduced due to disrupted GSIS of pancreatic islets. We first confirmed reduced plasma insulin levels, then investigated in vivo insulin secretion by glucose tolerance test and ex vivo GSIS of pancreatic islets in the presence of glucose at different doses, and KCl, glibenclamide and L-arginine...
August 28, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29023843/parameterization-of-the-gpr119-receptor-agonist-ar231453
#12
John Hamilton, Evangelia Kotsikorou
The GPR119 receptor is a class A G protein-coupled receptor expressed mainly in pancreatic beta cells. Since GPR119 receptor activation ameliorates Type 2 Diabetes through an increase in glucose-dependent insulin release, the development of new GPR119 receptor agonists would be worthwhile. A better understanding of the way agonists interact with the receptor would help to design better ligands for the receptor. It also would help to better understand the agonist mechanism of action. An understanding of how agonists interact with the receptor can be acquired using molecular dynamics simulations, which cannot be performed without having force field parameters for the ligand molecule...
October 12, 2017: Journal of Computational Chemistry
https://www.readbyqxmd.com/read/29022485/prevalence-of-%C3%AE-iii-tubulin-tubb3-expression-in-human-normal-tissues-and-cancers
#13
Fermín Person, Waldemar Wilczak, Claudia Hube-Magg, Christoph Burdelski, Christina Möller-Koop, Ronald Simon, Mercedes Noriega, Guido Sauter, Stefan Steurer, Susanne Burdak-Rothkamm, Frank Jacobsen
Microtubules are multifunctional cytoskeletal proteins that are involved in crucial cellular roles including maintenance of cell shape, intracellular transport, meiosis, and mitosis. Class III beta-tubulin (βIII-tubulin, also known as TUBB3) is a microtubule protein, normally expressed in cells of neuronal origin. Its expression was also reported in various other tumor types, such as several types of lung cancer, ovarian cancer, and esophageal cancer. TUBB3 is of clinical relevance as overexpression has been linked to poor response to microtubule-targeting anti-cancer drugs such as taxanes...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29018409/innate-viral-receptor-signaling-determines-type-1-diabetes-onset
#14
REVIEW
Zachary J Morse, Marc S Horwitz
Heritable susceptibility of the autoimmune disorder, type 1 diabetes (T1D), only partially equates for the incidence of the disease. Significant evidence attributes several environmental stressors, such as vitamin D deficiency, gut microbiome, dietary antigens, and most notably virus infections in triggering the onset of T1D in these genetically susceptible individuals. Extensive epidemiological and clinical studies have provided credibility to this causal relationship. Infection by the enterovirus, coxsackievirus B, has been closely associated with onset of T1D and is considered a significant etiological agent for disease induction...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29018156/the-effect-of-atorvastatin-on-pancreatic-beta-cell-requirement-in-women-with-polycystic-ovary-syndrome
#15
Thozhukat Sathyapalan, Anne-Marie Coady, Eric Kilpatrick, Stephen Atkin
BACKGROUND: There is an increased risk of developing T2DM in women with polycystic ovary syndrome (PCOS) and there is evidence that statins improve metabolic parameters in these patients. However, there is some data to show that statins increase the risk of incipient diabetes. MATERIAL AND METHODS: We have previously shown that 12-weeks of atorvastatin improves insulin resistance when measured using HOMA-IR. This post hoc-analysis was designed to look at the effect of atorvastatin on pancreatic β cell function using HOMA-β in the same study...
October 10, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28993759/the-four-way-stop-sign-viruses-12-lipoxygenase-islets-and-natural-killer-cells-in-type-1-diabetes-progression
#16
Michele L Semeraro, Lindsey M Glenn, Margaret A Morris
Natural killer (NK) cells represent an important effector arm against viral infection, and mounting evidence suggests that viral infection plays a role in the development of type 1 diabetes (T1D) in at least a portion of patients. NK cells recognize their target cells through a delicate balance of inhibitory and stimulatory receptors on their surface. If unbalanced, NK cells have great potential to wreak havoc in the pancreas due to the beta cell expression of the as-yet-defined NKp46 ligand through interactions with the activating NKp46 receptor found on the surface of most NK cells...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28993202/temporal-expression-profiling-of-plasma-proteins-reveals-oxidative-stress-in-early-stages-of-type-1-diabetes-progression
#17
Chih-Wei Liu, Lisa Bramer, Bobbie-Jo Webb-Robertson, Kathleen Waugh, Marian J Rewers, Qibin Zhang
Blood markers other than islet autoantibodies are greatly needed to indicate the pancreatic beta cell destruction process as early as possible, and more accurately reflect the progression of Type 1 Diabetes Mellitus (T1D). To this end, a longitudinal proteomic profiling of human plasma using TMT-10plex-based LC-MS/MS analysis was performed to track temporal proteomic changes of T1D patients (n=11) across 9 serial time points, spanning the period of T1D natural progression, in comparison with those of the matching healthy controls (n=10)...
October 6, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28993191/the-anti-aging-protein-klotho-is-induced-by-gaba-therapy-and-exerts-protective-and-stimulatory-effects-on-pancreatic-beta-cells
#18
Gérald J Prud'homme, Yelena Glinka, Merve Kurt, Wenjuan Liu, Qinghua Wang
Systemic gamma-aminobutyric acid (GABA) therapy prevents or ameliorates type 1 diabetes (T1D), by suppressing autoimmune responses and stimulating pancreatic beta cells. In beta cells, it increases insulin secretion, prevents apoptosis, and induces regeneration. It is unclear how GABA mediates these effects. We hypothesized that Klotho is involved. It is a multi-functional protein expressed in the kidneys, brain, pancreatic beta cells, other tissues, and is cell-bound or soluble. Klotho knockout mice display accelerated aging, and in humans Klotho circulating levels decline with age, renal disease and diabetes...
October 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28989066/interleukin-35-expression-correlates-with-microvessel-density-in-pancreatic-ductal-adenocarcinoma-recruits-monocytes-and-promotes-growth-and-angiogenesis-of-xenograft-tumors-in-mice
#19
Chongbiao Huang, Zengxun Li, Na Li, Yang Li, Antao Chang, Tiansuo Zhao, Xiuchao Wang, Hongwei Wang, Song Gao, Shengyu Yang, Jihui Hao, He Ren
BACKGROUND & AIMS: Cells of the monocyte lineage contribute to tumor angiogenesis. Interleukin 35 (IL35) is a member of the IL12 family produced by regulatory, but not effector, T cells. IL35 is a dimer comprising the IL12 alpha and IL27 beta chains, encoded by IL12A and EBI3, respectively. Expression of IL35 is increased in pancreatic ductal adenocarcinomas (PDACs) compared with normal pancreatic tissues, and promotes metastasis. We investigated the role of IL-35 in monocyte-induced angiogenesis of PDAC in mice...
October 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28984038/beta-cell-replacement-strategies-for-diabetes
#20
Timothy J Kieffer, Knut Woltjen, Kenji Osafune, Daisuke Yabe, Nobuya Inagaki
Diabetes is characterized by elevated levels of blood glucose as a result of insufficient production of insulin from loss or dysfunction of pancreatic islet beta cells. Here we review several approaches to replace beta cells that were recently discussed at a symposium held in Kyoto, Japan. Transplant of donor human islets can effectively treat diabetes and eliminate the need for insulin injections, supporting research aimed at identifying abundant supplies of cells. Studies demonstrating the feasibility of producing mouse islets in rats support the concept of generating pigs with human pancreas that can serve as donors of human islets, although scientific and ethical challenges remain...
October 6, 2017: Journal of Diabetes Investigation
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