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Pancreatic beta cells

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https://www.readbyqxmd.com/read/29227863/phenotypic-plasticity-in-the-pancreas-new-triggers-new-players
#1
REVIEW
Theoni Ingrid Demcollari, Ana-Maria Cujba, Rocio Sancho
The pancreas has a very limited regenerative potential during homeostasis. Despite its quiescent nature, recent in vivo models suggest a certain degree of regeneration and cellular interconversion is possible within the adult pancreas. It has now become evident that cellular plasticity can be observed in essentially all cell types within the pancreas when provided with the right stress stimuli. In this review, we will focus on the latest findings uncovering phenotypic plasticity of different cell types in the pancreas, the molecular mechanisms behind such plasticity and how plasticity associated with pancreatic or non-pancreatic cells could be harnessed in the generation of new insulin-producing beta cells...
December 8, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29226686/enhanced-specific-activity-by-multi-chelation-of-exendin-3-leads-to-improved-image-quality-and-in-vivo-beta-cell-imaging
#2
Lieke Joosten, Maarten Brom, Hanneke Peeters, Sandra Heskamp, Martin Behe, Otto C Boerman, Martin Gotthardt
OBJECTIVE: Glucagon like peptide-1 receptor (GLP-1R) targeting using radiolabeled exendin is a promising approach to non-invasively visualize and determine beta cell mass (BCM), which could help to unravel the pathophysiology of diabetes. However, saturation of the GLP-1R on beta cells occurs at low peptide doses, since the number of receptors expressed under physiological conditions is low. Therefore, tracers with high specific activities are required to sensitively image small variations in BCM...
December 11, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29226587/cellular-models-for-beta-cell-function-and-diabetes-gene-therapy
#3
REVIEW
Alastair D Green, Srividya Vasu, Peter R Flatt
Diabetes is characterised by the destruction and/or relative dysfunction of insulin secreting beta-cells in the pancreatic islets of Langerhans. Consequently, considerable effort has been made to understand the physiological processes governing insulin production and secretion in these cells, and to elucidate the mechanisms involved in their deterioration in the pathogenesis of diabetes. To date, considerable research has exploited clonal beta-cell lines derived from rodent insulinomas. Such cell-lines have proven to be a great asset in diabetes research, in vitro drug testing, and studies of beta-cell physiology; and provide a sustainable, and in many cases, more practical alternative to the use of animals or primary tissue...
December 11, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29224921/effects-of-acrylamide-on-oxidant-antioxidant-parameters-and-cyp2e1-expression-in-rat-pancreatic-endocrine-cells
#4
Jelena Marković, Milena Stošić, Danijela Kojić, Milica Matavulj
Oxidative stress is one of the principle mechanism of acrylamide-induced toxicity. Acrylamide is metabolized by cytochrome P450 2E1 (CYP2E1) to glycidamide or by direct conjugation with glutathione. Bearing in mind that up to now the effects of acrylamide on oxidative stress status and CYP2E1 level in endocrine pancreas have not been studied we performed qualitative and quantitative immunohistochemical evaluation of inducible nitric oxide synthase (iNOS), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2), catalase (CAT) and CYP2E1 expression in islets of Langerhans of rats subchronically treated with 25 or 50mg/kg bw of acrylamide...
December 7, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29224225/down-regulation-of-15-pgdh-by-interleukin-1-beta-from-activated-macrophages-leads-to-poor-prognosis-in-pancreatic-cancer
#5
Kota Arima, Yoshihiro Komohara, Luke Bu, Masayo Tsukamoto, Rumi Itoyama, Keisuke Miyake, Tomoyuki Uchihara, Yoko Ogata, Shigeki Nakagawa, Hirohisa Okabe, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Yo-Ichi Yamashita, Hideo Baba, Takatsugu Ishimoto
Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2 (PGE2 ). The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) degrades prostaglandin and is frequently decreased in several types of cancer; however, the molecular mechanisms of 15-PGDH suppression are unclear. The current study was conducted to elucidate the molecular mechanisms and clinical significance of 15-PGDH suppression in PDAC...
December 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/29223394/islet-%C3%AE-cell-an-endocrine-cell-secreting-mirnas
#6
Aisen Zhang, Dameng Li, Yucheng Liu, Jing Li, Yujing Zhang, Chen-Yu Zhang
The pancreas is an important endocrine organ. Pancreatic beta (β) cells secrete insulin to regulate the metabolism of glucose and maintain the stability of blood glucose. MicroRNAs (miRNAs), small (20-25 nt) non-coding RNA molecules, function in target gene silencing through post-transcriptional patterns, and multiple miRNAs regulate insulin secretion, insulin signaling pathways in pancreatic β cells and islet activity. In recent years, it has been found that many types of cells can secrete regulatory miRNA, but whether islet cells can secrete miRNA has not been clarified yet...
December 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29222788/rat-pancreatic-beta-cell-culture
#7
Myrian Velasco, Carlos Larqué, Carlos Manlio Díaz-García, Carmen Sanchez-Soto, Marcia Hiriart
In this chapter, we describe the methods used to culture mainly rat pancreatic beta cells. We consider necessary to use this approach to get more information about physiological, biophysical, and molecular biology characteristics of primary beta cells. Most of the literature published has been developed in murine and human beta-cell lines. However, there are many differences between tumoral cell lines and native cells because, in contrast to cell lines, primary cells do not divide. Moreover, cell lines can be in various stages of the cell cycle and thus have a different sensitivity to glucose, compared to primary cells...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29218453/energy-depletion-and-not-ros-formation-is-a-crucial-step-of-glucolipotoxicity-gltx-in-pancreatic-beta-cells
#8
Morgana Barroso Oquendo, Nikolas Layer, Rebecca Wagner, Peter Krippeit-Drews, Gisela Drews
We have shown previously that genetic or pharmacological deletion of KATP channels protect against beta cell dysfunction induced by reactive oxygen species (ROS). Since it is assumed that glucolipotoxicity (GLTx) causes ROS production, we aimed to evaluate whether suppression of KATP channel activity can also prevent beta cell damage evoked by GLTx. We used an in vitro model of GLTx and measured distinct parameters of stimulus-secretion coupling. GLTx gradually induced disturbances of Ca2+ oscillations over 3 days...
December 7, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29217654/the-p300-and-cbp-transcriptional-coactivators-are-required-for-beta-cell-and-alpha-cell-proliferation
#9
Chi Kin Wong, Adam K Wade-Vallance, Dan S Luciani, Paul K Brindle, Francis C Lynn, William T Gibson
p300 (EP300) and CBP (CREBBP) are transcriptional coactivators with histone acetyltransferase activity. Various beta cell transcription factors can recruit p300/CBP, and thus the coactivators could be important for beta cell function and health in vivo We hypothesized that p300/CBP contribute to the development and proper function of pancreatic islets. To test this, we bred and studied mice lacking p300/CBP in their islets. Mice lacking either p300 or CBP in islets developed glucose intolerance attributable to impaired insulin secretion, together with reduced alpha and beta cell area and islet insulin content...
December 7, 2017: Diabetes
https://www.readbyqxmd.com/read/29216879/anti-diabetic-potential-of-sapium-ellipticum-hochst-pax-leaf-extract-in-streptozotocin-stz-induced-diabetic-wistar-rats
#10
Osasenaga Macdonald Ighodaro, Oluseyi Adeboye Akinloye
BACKGOUND: Ethnobatanical survey associates Sapium ellipticum (SE) with antidiabetic usage among other medicinal functions in different parts of Africa. More importantly, previous studies on the plant extract in our laboratory showed that SE has significant effects on the activities of carbohydrate metabolizing enzymes such as glucokinase, glucose-6-phosphatase, α-amylase and α-glucosidase. In view of these, the anti-diabetic potential of the plant leaf extract in streptozotocin (STZ)-induced diabetes rat model (Wistar strain) was examined...
December 8, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29215945/the-adverse-effects-of-chronic-low-dose-exposure-to-nonylphenol-on-type-2-diabetes-mellitus-in-high-sucrose-high-fat-diet-treated-rats
#11
Jie Yu, Jin Yang, Ya Luo, Yang Mengxue, Wenmei Li, Yu Yang, Liting He, Jie Xu
OBJECTIVES: Although it has been shown that exposure to environmental endocrine disruptors (EDCs) has been implicated as a potential risk factor for metabolic disease, information on adverse effect of chronic low-dose exposure to nonylphenol (NP), on the development and progress of type 2 diabetes mellitus (T2DM) is scarce. NP, as an EDC, is a ubiquitous degradation product of nonylphenol polyethoxylate (NPE) that is primarily used in cleaning and industrial processes. METHOD: Eighty Sprague-Dawley rats were assigned into 8 groups (n = 10 per group): rats fed a normal-diet (ND) as the control (C-ND); rats fed a normal diet and were gavaged with NP at a dose level of 0...
December 7, 2017: Islets
https://www.readbyqxmd.com/read/29215791/protective-effects-of-carbonyl-iron-against-multiple-low-dose-streptozotocin-induced-diabetes-in-rodents
#12
Milica Vujicic, Tamara Saksida, Marija Mostarica Stojkovic, Neda Djedovic, Ivana Stojanovic, Stanislava Stosic-Grujicic
Particulate adjuvants have shown increasing promise as effective, safe and durable agents for the stimulation of immunity, or alternatively, the suppression of autoimmunity. Here we examined the potential of the adjuvant carbonyl iron (CI) for the modulation of organ-specific autoimmune disease - type 1 diabetes (T1D). T1D was induced by multiple low doses of streptozotocin (MLDS) that initiates beta cell death and triggers immune cell infiltration into the pancreatic islets. The results of this study indicate that the single in vivo application of CI to MLDS-treated DA rats, CBA/H mice, or C57BL/6 mice successfully counteracted the development of insulitis and hyperglycemia...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29214024/calcium-dependent-ultrasound-stimulation-of-secretory-events-from-pancreatic-beta-cells
#13
Ivan Suarez Castellanos, Tania Singh, Bogdan Balteanu, Diti Chatterjee Bhowmick, Aleksandar Jeremic, Vesna Zderic
Background: Our previous studies have indicated that ultrasound can stimulate the release of insulin from pancreatic beta cells, providing a potential novel treatment for type 2 diabetes. The purpose of this study was to explore the temporal dynamics and Ca2+-dependency of ultrasound-stimulated secretory events from dopamine-loaded pancreatic beta cells in an in vitro setup. Methods: Carbon fiber amperometry was used to detect secretion from INS-1832/13 beta cells in real time...
2017: Journal of Therapeutic Ultrasound
https://www.readbyqxmd.com/read/29208633/in-vivo-visualization-of-beta-cells-by-targeting-of-gpr44
#14
Olof Eriksson, Peter Johnström, Zsolt Cselenyi, Mahabuba Jahan, Ram K Selvaraju, Marianne Jensen-Waern, Akihiro Takano, Maria Sörhede Winzell, Christer Halldin, Stanko Skrtic, Olle Korsgren
GPR44 expression has recently been described as highly beta cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes.A radiolabeled small molecule GPR44 antagonist, [11C]AZ12204657, was evaluated for visualization of beta cells in pigs and non-human primates by Positron Emission Tomography (PET) as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from non-diabetic and diabetic subjects, in combination with insulin staining, was performed to assess beta cell selectivity of the radiotracer...
December 5, 2017: Diabetes
https://www.readbyqxmd.com/read/29208613/do-skeletal-muscle-secreted-factors-influence-the-function-of-pancreatic-beta-cells
#15
Jonathan P Barlow, Thomas P J Solomon
Skeletal muscle is an endocrine organ that secretes a variety of compounds including proteins (myokines), metabolites, microRNAs (miRNAs) and exosomes. Many of which are regulated by exercise and play important roles in endocrine signaling. Inter-organ communication via muscle-secreted factors therefore provides a novel area for investigation and implicates the importance of skeletal muscle in the pathophysiology of metabolic diseases such as type 2 diabetes (T2D). Given that underlying molecular mechanisms of T2D is subject of ongoing research, in light of new evidence, it is probable that inter-organ crosstalk between skeletal muscle and pancreatic beta-cells (β-cells) plays an important part...
December 5, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29208420/the-inhibitor-of-connexin-cx36-channels-mefloquine-inhibits-voltage-dependent-ca2-channels-and-insulin-secretion
#16
Nele Seemann, Andrea Welling, Ingo Rustenbeck
The antimalarial agent, mefloquine, inhibits the function of connexin Cx36 gap junctions and hemichannels and has thus become a tool to investigate their physiological relevance in pancreatic islets. In view of earlier reports on a KATP channel-block by mefloquine, the specificity of mefloquine as a pharmacological tool was investigated. Mouse pancreatic islets and single beta cells were used to measure membrane potential, whole cell currents, Ca2+ channel activity, cytosolic Ca2+ concentration ([Ca2+]i) and insulin secretion...
December 2, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29207798/does-vitamin-d-supplementation-improve-glycaemic-control-in-children-with-type-1-diabetes-mellitus-a-randomized-controlled-trial
#17
Shreya Sharma, Niranjan Biswal, Adhisivam Bethou, Medha Rajappa, Sadish Kumar, Vickneshwaran Vinayagam
Introduction: Vitamin D endocrine system is a potential immune system modulator and has been implicated in the pathogenesis of several autoimmune diseases including Type 1 Diabetes Mellitus (T1DM). Studies have demonstrated an inverse risk relationship between T1DM and Vitamin D levels and also, shown a reduced risk of the disease with its supplementation. Aim: To evaluate the role of Vitamin D as an adjuvant in improving glycaemic control and residual pancreatic beta-cell function...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/29207597/inhibition-of-miro1-disturbs-mitophagy-and-pancreatic-%C3%AE-cell-function-interfering-insulin-release-via-irs-akt-foxo1-in-diabetes
#18
Lingling Chen, Chunyan Liu, Jianfeng Gao, Zhiwen Xie, Lawrence W C Chan, Damien J Keating, Yibin Yang, Jiazhong Sun, Fuling Zhou, Yongchang Wei, Xiuli Men, Sijun Yang
Mitochondrial function is essential to meet metabolic demand of pancreatic beta cells respond to high nutrient stress. Mitophagy is an essential component to normal pancreatic β-cell function and has been associated with β-cell failure in Type 2 diabetes (T2D). Our previous studies have indicated that mitochondrial Rho (Miro) GTPase-mediated mitochondrial dysfunction under high nutrient stress leads to NOD-like receptor 3 (NLRP3)-dependent proinflammatory responses and subsequent insulin resistance. However, the in vivo mechanism by which Miro1 underlies mitophagy has not been identified...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29203512/glucocorticoids-reprogram-beta-cell-signaling-to-preserve-insulin-secretion
#19
Nicholas H F Fine, Craig L Doig, Yasir S Elhassan, Nicholas C Vierra, Piero Marchetti, Marco Bugliani, Rita Nano, Lorenzo Piemonti, Guy A Rutter, David A Jacobson, Gareth G Lavery, David J Hodson
Excessive glucocorticoid exposure has been shown to be deleterious for pancreatic beta cell function and insulin release. However, glucocorticoids at physiological levels are essential for many homeostatic processes, including glycemic control. Here, we show that corticosterone and cortisol and their less active precursors, 11-dehydrocorticosterone (11-DHC) and cortisone, suppress voltage-dependent Ca2+ channel function and Ca2+ fluxes in rodent as well as human beta cells. However, insulin secretion, maximal ATP/ADP responses to glucose and beta cell identity were all unaffected...
December 4, 2017: Diabetes
https://www.readbyqxmd.com/read/29198674/external-validation-of-the-newly-developed-beta-2-scoring-system-for-pancreatic-islet-graft-function-assessment
#20
J Gołębiewska, J Solomina, M R Kijek, A Kotukhov, L Basto, K Gołąb, P J Bachul, E Konsur, K Ciepły, N Fillman, L-J Wang, C C Thomas, L H Philipson, M Tibudan, A Krenc, A Dębska-Ślizień, J Fung, P Witkowski
BACKGROUND: BETA-2 score using a single fasting blood sample was developed to estimate beta-cell function after islet transplantation (ITx) and was validated internally by a high ITx volume center (Edmonton). The goal was to validate BETA-2 externally, in our center. METHODS: Areas under receiver operating characteristic curves (AUROCs) were obtained to see if beta score or BETA-2 would better detect insulin independence and glucose intolerance. RESULTS: We analyzed values from 48 mixed meal tolerance tests (MMTTs) in 4 ITx recipients with a long-term follow-up to 140 months (LT group) and from 54 MMTTs in 13 short-term group patients (ST group)...
December 2017: Transplantation Proceedings
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