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https://www.readbyqxmd.com/read/29320741/endocytosis-of-katp-channels-drives-glucose-stimulated-excitation-of-pancreatic-%C3%AE-cells
#1
Young-Eun Han, Jung Nyeo Chun, Min Jeong Kwon, Young-Sun Ji, Myong-Ho Jeong, Hye-Hyun Kim, Sun-Hyun Park, Jong Cheol Rah, Jong-Sun Kang, Suk-Ho Lee, Won-Kyung Ho
Insulin secretion from pancreatic β cells in response to high glucose (HG) critically depends on the inhibition of KATP channel activity in HG. It is generally believed that HG-induced effects are mediated by the increase in intracellular ATP, but here, we showed that, in INS-1 cells, endocytosis of KATP channel plays a major role. Upon HG stimulation, resting membrane potential depolarized by 30.6 mV (from -69.2 to -38.6 mV) and KATP conductance decreased by 91% (from 0.243 to 0.022 nS/pF), whereas intracellular ATP was increased by only 47%...
January 9, 2018: Cell Reports
https://www.readbyqxmd.com/read/29305569/emergence-of-insulin-resistance-following-empirical-glibenclamide-therapy-a-case-report-of-neonatal-diabetes-with-a-recessive-ins-gene-mutation
#2
Melek Yildiz, Teoman Akcay, Banu Aydin, Abdurrahman Akgun, Beyza Belde Dogan, Elisa De Franco, Sian Ellard, Hasan Onal
BACKGROUND: As KATP channel mutations are the most common cause of neonatal diabetes mellitus (NDM) and patients with these mutations can be treated with oral sulfonylureas, empiric therapy is a common practice for NDM patients. CASE PRESENTATION: A non-syndromic, small for gestational age baby born to first-degree consanguineous parents was diagnosed with NDM. Because of hypo- and hyperglycemic episodes and variability in insulin requirement, we initiated a trial of glibenclamide, with a presumptive diagnosis of NDM caused by a KATP channel mutation...
January 6, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/29296240/sulfonylurea-for-the-treatment-of-neonatal-diabetes-owing-to-katp-channel-mutations-a-systematic-review-and-meta-analysis
#3
Hongliang Zhang, Xiaobin Zhong, Zhenguang Huang, Chun Huang, Taotao Liu, Yue Qiu
The effect of sulfonylurea for the treatment of neonatal diabetes (NDM) is remain uncertain. We conducted this systematic review and meta-analysis to investigate the effect of sulfonylurea for NDM and to provide the latest and most convincing evidence for developing clinical practice guidelines of NDM. A literature review was performed to identify all published studies reporting the sulfonylurea on the treatment of neonatal diabetes. The search included the following databases: PUBMED, EMBASE and the Cochrane Library...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286281/molecular-structure-of-human-katp-in-complex-with-atp-and-adp
#4
Kenneth Pak Kin Lee, Jue Chen, Roderick MacKinnon
In many excitable cells KATP channels respond to intracellular adenosine nucleotides: ATP inhibits while ADP activates. We present two structures of the human pancreatic KATP channel, containing the ABC transporter SUR1 and the inward-rectifier K+ channel Kir6.2, in the presence of Mg2+ and nucleotides. These structures, referred to as quatrefoil and propeller forms, were determined by single-particle cryo-EM at 3.9 Å and 5.6 Å, respectively. In both forms ATP occupies the inhibitory site in Kir6.2. The nucleotide-binding domains of SUR1 are dimerized with Mg2+-ATP in the degenerate site and Mg2+-ADP in the consensus site...
December 29, 2017: ELife
https://www.readbyqxmd.com/read/29281328/altered-potassium-ion-channel-function-as-a-possible-mechanism-of-increased-blood-pressure-in-rats-fed-thermally-oxidized-palm-oil-diets
#5
Etah E Nkanu, Daniel U Owu, Eme E Osim
Intake of thermally oxidized palm oil leads to cytotoxicity and alteration of the potassium ion channel function. This study investigated the effects of fresh and thermally oxidized palm oil diets on blood pressure and potassium ion channel function in blood pressure regulation. Male Wistar rats were randomly divided into three groups of eight rats. Control group received normal feed; fresh palm oil (FPO) and thermally oxidized palm oil (TPO) groups were fed a diet mixed with 15% (weight/weight) fresh palm oil and five times heated palm oil, respectively, for 16 weeks...
December 27, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/29275331/cantu-syndrome-associated-sur2-abcc9-mutations-in-distinct-structural-domains-result-in-katp-channel-gain-of-function-by-differential-mechanisms
#6
Conor McClenaghan, Alex Hanson, Monica Sala-Rabanal, Helen I Roessler, Dragana Josifova, Dorothy K Grange, Gijs van Haaften, Colin G Nichols
The complex cardiovascular disorder Cantu syndrome (CS) arises from gain-of-function mutations in either KCNJ8 or ABCC9, the genes encoding the Kir6.1 and SUR2 subunits of ATP-sensitive potassium (KATP) channels, respectively. Recent reports indicate that such mutations can increase channel activity by multiple molecular mechanisms. In this study, we determined the mechanism by which KATP function is altered by several substitutions in distinct structural domains of SUR2: D207E in the intracellular L0-linker and Y985S, G989E, M1060I, and R1154Q/W in TMD2...
December 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29260608/tonic-regulation-of-middle-meningeal-artery-diameter-by-atp-sensitive-potassium-channels
#7
Arsalan U Syed, Masayo Koide, Joseph E Brayden, George C Wellman
Activation of ATP-sensitive potassium (KATP) channels in arterial smooth muscle (ASM) contributes to vasodilation evoked by a variety of endogenous and exogenous compounds. Although controversial, activation of KATP channels by neuropeptides such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating peptide (PACAP) in the trigeminovascular system, including the middle meningeal artery (MMA), has been linked to migraine headache. The objective of the current study was to determine if ongoing KATP channel activity also influences MMA diameter...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29223124/activation-of-mitochondrial-katp-channels-mediates-neuroprotection-induced-by-chronic-morphine-preconditioning-in-hippocampal-ca-1-neurons-following-cerebral-ischemia
#8
Maedeh Arabian, Nahid Aboutaleb, Mansoureh Soleimani, Marjan Ajami, Rouhollah Habibey, Hamidreza Pazoki-Toroudi
PURPOSE: Pharmacologic preconditioning, through activating several mechanisms and mediators, can increase the tolerance of different tissues against ischemia/reperfusion (I/R) injury. Recent studies have shown that morphine preconditioning has protective effects in different organs, especially in the heart. Nevertheless, its mechanisms are not well elucidated in the brain. The present study aimed to clarify whether the activation of mitochondrial KATP (mKATP) channels in chronic morphine (CM) preconditioning could decrease hippocampus damage following I/R injury...
December 6, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/29218453/energy-depletion-and-not-ros-formation-is-a-crucial-step-of-glucolipotoxicity-gltx-in-pancreatic-beta-cells
#9
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/29215951/regulation-of-aqueous-humor-dynamics-by-hydrogen-sulfide-potential-role-in-glaucoma-pharmacotherapy
#10
Sunny E Ohia, Jenaye Robinson, Leah Mitchell, Kalu K Ngele, Segewkal Heruye, Catherine A Opere, Ya Fatou Njie-Mbye
Hydrogen sulfide (H2S) is a gaseous transmitter with well-known biological actions in a wide variety of tissues and organs. The potential involvement of this gas in physiological and pathological processes in the eye has led to several in vitro, ex vivo, and in vivo studies to understand its pharmacological role in some mammalian species. Evidence from literature demonstrates that 4 enzymes responsible for the biosynthesis of this gas (cystathionine β-synthase, CBS; cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3MST; and d-amino acid oxidase) are present in the cornea, iris, ciliary body, lens, and retina...
December 7, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29211322/perivascular-adipose-tissue-and-the-dynamic-regulation-of-kv-7-and-kir-channels-implications-to-resistant-hypertension
#11
Maik Gollasch, Donald G Welsh, Rudolf Schubert
Resistant hypertension is defined as high blood pressure that remains uncontrolled despite treatment with at least three antihypertensive drugs at adequate doses. Resistant hypertension is an increasingly common clinical problem in older age, obesity, diabetes, sleep apnea, and chronic kidney disease. Although the direct vasodilator minoxidil was introduced in the early 1970s, only recently has this drug been shown to be particularly effective in a subgroup of patients with treatment-resistant or uncontrolled hypertension...
December 6, 2017: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
https://www.readbyqxmd.com/read/29208420/the-inhibitor-of-connexin-cx36-channels-mefloquine-inhibits-voltage-dependent-ca2-channels-and-insulin-secretion
#12
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/29205356/molecular-and-functional-characterization-of-inwardly-rectifying-k-currents-in-murine-proximal-colon
#13
Xu Huang, Si Hyung Lee, Hongli Lu, Kenton M Sanders, Sang Don Koh
Membrane potentials of gastrointestinal (GI) muscles are important because voltage dependent Ca2+ channels in smooth muscle cells (SMC) provide the Ca2+ that triggers contraction. Regulation of membrane potential is complicated because SMC are electrically coupled to interstitial cells of Cajal (ICC) and PDGFRα+ cells. Activation of conductances in any of these cells affects the excitability of the syncytium. We explored the role of inward rectifier K+ conductances in colonic ICC that might contribute to regulation of membrane potential...
December 3, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29200726/influence-of-flavonoids-on-mechanism-of-modulation-of-insulin-secretion
#14
Juliana Mikaelly Dias Soares, Ana Ediléia Barbosa Pereira Leal, Juliane Cabral Silva, Jackson R G S Almeida, Helinando Pequeno de Oliveira
Background: The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue. Objective: To study the influence of flavonoid on overall modulation mechanisms of insulin secretion. Methods: The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29197370/tocolytic-action-and-underlying-mechanism-of-galetin-3-6-dimethyl-ether-on-rat-uterus
#15
Juliana da Nóbrega Carreiro, Iara Leão Luna de Souza, Joedna Cavalcante Pereira, Luiz Henrique César Vasconcelos, Rafael de Almeida Travassos, Barbara Viviana de Oliveira Santos, Bagnólia Araújo da Silva
BACKGROUND: Galetin 3,6-dimethyl ether (FGAL) is a flavonoid isolated from aerial parts of Piptadenia stipulacea. Previously, FGAL was shown to inhibit both carbachol- and oxytocin-induced phasic contractions in the rat uterus, which was more potent with oxytocin. Thus, in this study, we aimed to investigate the tocolytic action mechanism of FGAL on the rat uterus. METHODS: Segments of rat uterus ileum were suspended in organ bath containing modified Locke-Ringer solution at 32 °C, bubbled with carbogen mixture under a resting tension of 1 g...
December 2, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29193528/-epicatechin-induced-relaxation-of-isolated-human-saphenous-vein-roles-of-k-and-ca2-channels
#16
Marija Marinko, Goran Jankovic, Dragoslav Nenezic, Predrag Milojevic, Ivan Stojanovic, Vladimir Kanjuh, Aleksandra Novakovic
In this study, we aimed to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human saphenous vein (HSV), as a part of its cardioprotective action, and to define the mechanisms underlying this vasorelaxation. (-)-Epicatechin induced a concentration-dependent relaxation of HSV pre-contracted by phenylephrine. Among K+ channel blockers, 4-aminopyridine, margatoxin, and iberiotoxin significantly inhibited relaxation of HSV, while glibenclamide considerably reduced effects of the high concentrations of (-)-epicatechin...
November 29, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29188640/-role-of-adenosine-triphosphate-sensitive-potassium-channel-in-hydrogen-sulfide-induced-inhibition-of-high-glucoseinduced-osteoblast-damage
#17
Liu Yuanyuan, Guan Xiumei, Cheng Min, Li Xin, Pan Yueyang, Guo Zhiliang
OBJECTIVE: The aim of this study is to identify the role of adenosine triphosphate-sensitive potassium channel (KATP) in hydrogen sulfide (H₂S)-induced inhibition of high glucose (HG)-induced osteoblast damage. METHODS: Osteoblasts from rat mandible were cultured and identified. The osteoblasts were then treated with HG, H₂S, KATP channel opener pinacidil (Pia), and KATP channel blocker glibenclamide (Gli). Western blot method was performed to detect the expression of KATP channel protein...
October 1, 2017: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/29185069/connexin-43-and-atp-sensitive-potassium-channels-crosstalk-a-missing-link-in-hypoxia-ischemia-stress
#18
REVIEW
Ajaz Ahmad Waza, Shabir Ahmad Bhat, Mahboob Ul Hussain, Bashir A Ganai
Connexin 43 (Cx43) is a gap junction protein expressed in various tissues and organs of vertebrates. Besides functioning as a gap junction, Cx43 also regulates diverse cellular processes like cell growth and differentiation, cell migration, cell survival, etc. Cx43 is critical for normal cardiac functioning and is therefore abundantly expressed in cardiomyocytes. On the other hand, ATP-sensitive potassium (KATP) channels are metabolic sensors converting metabolic changes into electrical activity. These channels are important in maintaining the neurotransmitter release, smooth muscle relaxation, cardiac action potential repolarization, normal physiology of cellular repolarization, insulin secretion and immune function...
November 29, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29184506/recent-advances-in-the-cellular-and-molecular-mechanisms-of-hypothalamic-neuronal-glucose-detection
#19
Xavier Fioramonti, Chloé Chrétien, Corinne Leloup, Luc Pénicaud
The hypothalamus have been recognized for decades as one of the major brain centers for the control of energy homeostasis. This area contains specialized neurons able to detect changes in nutrients level. Among them, glucose-sensing neurons use glucose as a signaling molecule in addition to its fueling role. In this review we will describe the different sub-populations of glucose-sensing neurons present in the hypothalamus and highlight their nature in terms of neurotransmitter/neuropeptide expression. This review will particularly discuss whether pro-opiomelanocortin (POMC) neurons from the arcuate nucleus are directly glucose-sensing...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29183106/monogenic-diabetes-not-caused-by-mutations-in-mody-genes-a-very-heterogenous-group-of-diabetes
#20
Zeynep Şıklar, Elisa de Franco, Matthew B Johnson, Sarah E Flanagan, Sian Ellard, Serdar Ceylaner, Kaan Boztuğ, Figen Doğu, Aydan İkincioğulları, Zarife Kuloğlu, Aydan Kansu, Merih Berberoğlu
Monogenic diabetes represents a heterogeneous group of disorders resulting from a single gene defect leading to disruption of insulin secretion or a reduction in the number of beta cells. Despite the classification of monogenic diabetes into neonatal diabetes or maturity onset diabetes of the young (MODY) according to age of onset, not every case can be classified into those 2 groups. We evaluated patients with monogenic diabetes diagnosed during the last 10 year period. Type 1 DM, MODY, and patients with negative autoantibodies and no mutation in a known gene were excluded from the study...
November 28, 2017: Experimental and Clinical Endocrinology & Diabetes
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