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https://www.readbyqxmd.com/read/28906027/sur1-trpm4-and-aqp4-form-a-heteromultimeric-complex-that-amplifies-ion-water-osmotic-coupling-and-drives-astrocyte-swelling
#1
Jesse A Stokum, Min S Kwon, Seung K Woo, Orest Tsymbalyuk, Rudi Vennekens, Volodymyr Gerzanich, J Marc Simard
Astrocyte swelling occurs after central nervous system injury and contributes to brain swelling, which can increase mortality. Mechanisms proffered to explain astrocyte swelling emphasize the importance of either aquaporin-4 (AQP4), an astrocyte water channel, or of Na(+) -permeable channels, which mediate cellular osmolyte influx. However, the spatio-temporal functional interactions between AQP4 and Na(+) -permeable channels that drive swelling are poorly understood. We hypothesized that astrocyte swelling after injury is linked to an interaction between AQP4 and Na(+) -permeable channels that are newly upregulated...
September 14, 2017: Glia
https://www.readbyqxmd.com/read/28877214/direct-versus-indirect-actions-of-ghrelin-on-hypothalamic-npy-neurons
#2
Hiroshi Hashiguchi, Zhenyu Sheng, Vanessa Routh, Volodymyr Gerzanich, J Marc Simard, Joseph Bryan
OBJECTIVES: Assess direct versus indirect action(s) of ghrelin on hypothalamic NPY neurons. MATERIALS AND METHODS: Electrophysiology was used to measure ion channel activity in NPY-GFP neurons in slice preparations. Ca2+ imaging was used to monitor ghrelin activation of isolated NPY GFP-labeled neurons. Immunohistochemistry was used to localize Trpm4, SUR1 and Kir6.2 in the hypothalamus. RESULTS: Acylated ghrelin depolarized the membrane potential (MP) of NPY-GFP neurons in brain slices...
2017: PloS One
https://www.readbyqxmd.com/read/28865458/salutary-effects-of-glibenclamide-during-the-chronic-phase-of-murine-experimental-autoimmune-encephalomyelitis
#3
Volodymyr Gerzanich, Tapas K Makar, Poornachander Reddy Guda, Min Seong Kwon, Jesse A Stokum, Seung Kyoon Woo, Svetlana Ivanova, Alexander Ivanov, Rupal I Mehta, Alexandra Brooke Morris, Joseph Bryan, Christopher T Bever, J Marc Simard
BACKGROUND: In multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), inflammation is perpetuated by both infiltrating leukocytes and astrocytes. Recent work implicated SUR1-TRPM4 channels, expressed mostly by astrocytes, in murine EAE. We tested the hypothesis that pharmacological inhibition of SUR1 during the chronic phase of EAE would be beneficial. METHODS: EAE was induced in mice using myelin oligodendrocyte glycoprotein (MOG) 35-55. Glibenclamide (10 μg/day) was administered beginning 12 or 24 days later...
September 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28864549/atrial-natriuretic-peptide-anp-affects-stimulus-secretion-coupling-of-pancreatic-%C3%AE-cells
#4
Sabrina Undank, Julia Kaiser, Jelena Sikimic, Martina Düfer, Peter Krippeit-Drews, Gisela Drews
ANP influences glucose homeostasis and possibly acts as a link between the cardiovascular system and metabolism, especially in metabolic disorders like diabetes. The present study aimed to evaluate effects of ANP on β-cell function by the use of a β-cell specific knockout of the ANP receptor with guanylate cyclase activity (βGC-A-KO). ANP augmented insulin secretion at the threshold glucose concentration of 6 mM and decreased KATP single channel activity in β-cells of control mice but not of βGC-A-KO mice...
September 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28749940/upregulation-of-an-inward-rectifying-k-channel-can-rescue-slow-ca2-oscillations-in-k-atp-channel-deficient-pancreatic-islets
#5
Vehpi Yildirim, Suryakiran Vadrevu, Benjamin Thompson, Leslie S Satin, Richard Bertram
Plasma insulin oscillations are known to have physiological importance in the regulation of blood glucose. In insulin-secreting β-cells of pancreatic islets, K(ATP) channels play a key role in regulating glucose-dependent insulin secretion. In addition, they convey oscillations in cellular metabolism to the membrane by sensing adenine nucleotides, and are thus instrumental in mediating pulsatile insulin secretion. Blocking K(ATP) channels pharmacologically depolarizes the β-cell plasma membrane and terminates islet oscillations...
July 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28748494/high-glucose-stimulates-cell-proliferation-and-collagen-iv-production-in-rat-mesangial-cells-through-inhibiting-ampk-katp-signaling
#6
Bei Zhang, Yong-Quan Shi, Jun-Jie Zou, Xiang-Fang Chen, Wei Tang, Fei Ye, Zhi-Min Liu
PURPOSE: The present study investigated the putative mechanisms underlying effects of KATP channel on high glucose (HG)-induced mesangial cell proliferation and tissue inhibitors of metalloproteinases (TIMP)-2 and Collagen IV production. METHODS: Rat mesangial cells were subjected to whole cell patch clamp to record the KATP channel currents under high glucose (HG, 30 mM) condition. Cell proliferation was measured using a CCK-8 assay. The production of TIMP-2 and Collagen IV and AMP-activated protein kinase (AMPK)-signaling pathway activity was assessed by ELISA and Western blotting, respectively...
July 26, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28740332/a-protective-role-of-glibenclamide-in-inflammation-associated-injury
#7
REVIEW
Gensheng Zhang, Xiuhui Lin, Shufang Zhang, Huiqing Xiu, Chuli Pan, Wei Cui
Glibenclamide is the most widely used sulfonylurea drug for the treatment of type 2 diabetes mellitus (DM). Recent studies have suggested that glibenclamide reduced adverse neuroinflammation and improved behavioral outcomes following central nervous system (CNS) injury. We reviewed glibenclamide's anti-inflammatory effects: abundant evidences have shown that glibenclamide exerted an anti-inflammatory effect in respiratory, digestive, urological, cardiological, and CNS diseases, as well as in ischemia-reperfusion injury...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28731533/improvement-of-d-lactic-acid-production-in-saccharomyces-cerevisiae-under-acidic-conditions-by-evolutionary-and-rational-metabolic-engineering
#8
Seung-Ho Baek, Eunice Y Kwon, Sang-Jeong Bae, Bo-Ram Cho, Seon-Young Kim, Ji-Sook Hahn
Microbial lactic acid (LA) production under acidic fermentation conditions is favorable to reduce the production cost, but circumventing LA toxicity is a major challenge. We generated D-LA-producing Saccharomyces cerevisiae strain JHY5610 by expressing D-lactate dehydrogenase gene (Lm. ldhA) from Leuconostoc mesenteroides, while deleting genes involved in ethanol production (ADH1, ADH2, ADH3, ADH4, and ADH5), glycerol production (GPD1 and GPD2), and degradation of D-LA (DLD1). Adaptive laboratory evolution of JHY5610 led to a strain JHY5710 having higher LA tolerance and D-LA-production capability...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28672904/katp-channels-in-high-glucose-induced-rat-mesangial-cell-proliferation-and-release-of-mmp-2-and-fibronectin
#9
Bei Zhang, Yongquan Shi, Junjie Zou, Xiangfang Chen, Wei Tang, Fei Ye, Zhimin Liu
ATP-sensitive potassium (KATP) channels are well characterized in cardiac, pancreatic and many other muscle cells. The purpose of this study was to determine if KATP channels play a role in diabetic nephropathy (DN). In the present study, functional expression of the KATP channel was examined in rat mesangial cells with or without high glucose (HG) stimulation. The mesangial cell proliferation and the release of matrix metalloproteinase (MMP)-2 and fibronectin in response to high glucose with a selective opener of KATP (diazoxide, DZX), or with a selective inhibitor of KATP (5-hydroxydecanoate, 5-HD) were also measured...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28663158/an-abcc8-nonsense-mutation-causing-neonatal-diabetes-through-altered-transcript-expression
#10
Sarah E Flanagan, Vũ Chí Dũng, Jayne A L Houghton, Elisa De Franco, Can Thi Bich Ngoc, Annet Damhuis, Frances M Ashcroft, Lorna W Harries, Sian Ellard
The pancreatic ATP-sensitive K+ (K-ATP) channel is a key regulator of insulin secretion. Gain-of-function mutations in the genes encoding the Kir6.2 (KCNJ11) and SUR1 (ABCC8) subunits of the channel cause neonatal diabetes, whilst loss-of-function mutations in these genes result in congenital hyperinsulinism. We report two patients with neonatal diabetes in whom we unexpectedly identified recessively inherited loss-of-function mutations. The aim of this study was to investigate how a homozygous nonsense mutation in ABCC8 could result in neonatal diabetes...
September 1, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28662892/glibenclamide-pretreatment-protects-against-chronic-memory-dysfunction-and-glial-activation-in-rat-cranial-blast-traumatic-brain-injury
#11
Jesse A Stokum, Kaspar Keledjian, Erik Hayman, Jason K Karimy, Adam Pampori, Ziyan Imran, Seung Kyoon Woo, Volodymyr Gerzanich, J Marc Simard
Blast traumatic brain injury (bTBI) affects both military and civilian populations, and often results in chronic deficits in cognition and memory. Chronic glial activation after bTBI has been linked with cognitive decline. Pharmacological inhibition of sulfonylurea receptor 1 (SUR1) with glibenclamide was shown previously to reduce glial activation and improve cognition in contusive models of CNS trauma, but has not been examined in bTBI. We postulated that glibenclamide would reduce chronic glial activation and improve long-term memory function after bTBI...
June 27, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28600547/modeling-congenital-hyperinsulinism-with-abcc8-deficient-human-embryonic-stem-cells-generated-by-crispr-cas9
#12
Dongsheng Guo, Haikun Liu, Aynisahan Ruzi, Ge Gao, Abbas Nasir, Yanli Liu, Fan Yang, Feima Wu, Guosheng Xu, Yin-Xiong Li
Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by excess insulin secretion, which results in hypoglycemia. Mutation of sulfonylurea receptor 1 (SUR1), encoded by the ABCC8 gene, is the main cause of CHI. Here, we captured the phenotype of excess insulin secretion through pancreatic differentiation of ABCC8-deficient stem cells generated by the CRISPR/Cas9 system. ABCC8-deficient insulin-producing cells secreted higher insulin than their wild-type counterparts, and the excess insulin secretion was rescued by nifedipine, octreotide and nicorandil...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28587604/kcnj11-abcc8-and-tcf7l2-polymorphisms-and-the-response-to-sulfonylurea-treatment-in-patients-with-type-2-diabetes-a-bioinformatics-assessment
#13
Jingwen Song, Yunzhong Yang, Franck Mauvais-Jarvis, Yu-Ping Wang, Tianhua Niu
BACKGROUND: Type 2 diabetes (T2D) is a worldwide epidemic with considerable health and economic consequences. Sulfonylureas are widely used drugs for the treatment of patients with T2D. KCNJ11 and ABCC8 encode the Kir6.2 (pore-forming subunit) and SUR1 (regulatory subunit that binds to sulfonylurea) of pancreatic β cell KATP channel respectively with a critical role in insulin secretion and glucose homeostasis. TCF7L2 encodes a transcription factor expressed in pancreatic β cells that regulates insulin production and processing...
June 6, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28540314/neonatal-diabetes-case-report-of-a-9-week-old-presenting-diabetic-ketoacidosis-due-to-an-activating-abcc8-gene-mutation
#14
Shawn Sood, Hannah Landreth, Jessee Bustinza, Laura Chalmers, Roopa Thukaram
Context: Neonatal diabetes mellitus, a rare condition occurring in approximately 1 in 500 000 live births, is defined as insulin-requiring hyperglycemia presenting in the first months of life. Neonatal diabetes can be transient or permanent, with studies characterizing the condition as a monogenic disorder. Case Report: We describe a case of a 9-week-old infant with neonatal diabetes who presented in diabetic ketoacidosis due to a mutation affecting the ABCC8 gene that encodes the SUR1 subunit of the potassium ATP channel...
January 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28483598/the-mechano-sensitivity-of-cardiac-atp-sensitive-potassium-channels-is-mediated-by-intrinsic-mgatpase-activity
#15
Mohammad Fatehi, Christian C Carter, Nermeen Youssef, Peter E Light
Cardiac ATP-sensitive K(+) (KATP) channel activity plays an important cardio-protective role in regulating excitability in response to metabolic stress. Evidence suggests that these channels are also mechano-sensitive and therefore may couple KATP channel activity to increased cardiac workloads. However, the molecular mechanism that couples membrane stretch to channel activity is not currently known. We hypothesized that membrane stretch may alter the intrinsic MgATPase activity of the cardiac KATP channel resulting in increased channel activation...
May 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28412320/glibenclamide-ameliorates-cerebral-edema-and-improves-outcomes-in-a-rat-model-of-status-epilepticus
#16
Zhenzhou Lin, Hua Huang, Yong Gu, Kaibin Huang, Yafang Hu, Zhong Ji, Yongming Wu, Shengnan Wang, Tingting Yang, Suyue Pan
Glibenclamide (GBC), a sulfonylurea receptor 1 blocker, emerges recently as a promising neuron protectant in various neurological disorders. This study aimed to determine whether GBC improves survival and neurological outcome of status epilepticus (SE). Male Sprague-Dawley rats successfully undergoing SE for 2.5 h (n = 134) were randomly assigned to GBC or vehicle group. Rats in the GBC group received a loading dose of 10 μg/kg of GBC, followed by 1.2 μg/6 h for 3 days, while same dose of vehicle was used as control...
July 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28377630/katp-channels-mediate-differential-metabolic-responses-to-glucose-shortage-of-the-dorsomedial-and-ventrolateral-oscillators-in-the-central-clock
#17
Jyh-Jeen Yang, Ruo-Ciao Cheng, Pi-Cheng Cheng, Yi-Chi Wang, Rong-Chi Huang
The suprachiasmatic nucleus (SCN) central clock comprises two coupled oscillators, with light entraining the retinorecipient vasoactive intestinal peptide (VIP)-positive ventrolateral oscillator, which then entrains the arginine vasopressin (AVP)-positive dorsomedial oscillator. While glucose availability is known to alter photic entrainment, it is unclear how the SCN neurones respond to metabolic regulation and whether the two oscillators respond differently. Here we show that the ATP-sensitive K(+) (KATP) channel mediates differential responses to glucose shortage of the two oscillators...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28349071/forkhead-protein-foxo1-acts-as-a-repressor-to-inhibit-cell-differentiation-in-human-fetal-pancreatic-progenitor-cells
#18
Zongzhe Jiang, Jingjing Tian, Wenjian Zhang, Hao Yan, Liping Liu, Zhenhe Huang, Jinning Lou, Xiaosong Ma
Our colleagues have reported previously that human pancreatic progenitor cells can readily differentiate into insulin-containing cells. Particularly, transplantation of these cell clusters upon in vitro induction for 3-4 w partially restores hyperglycemia in diabetic nude mice. In this study, we used human fetal pancreatic progenitor cells to identify the forkhead protein FoxO1 as the key regulator for cell differentiation. Thus, induction of human fetal pancreatic progenitor cells for 1 week led to increase of the pancreatic β cell markers such as Ngn3, but decrease of stem cell markers including Oct4, Nanog, and CK19...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28346775/hyperinsulinism-causing-mutations-cause-multiple-molecular-defects-in-sur1-nbd1
#19
Claudia P Alvarez, Marijana Stagljar, D Ranjith Muhandiram, Voula Kanelis
The sulfonylurea receptor 1 (SUR1) protein forms the regulatory subunit in ATP sensitive K(+) (KATP) channels in the pancreas. SUR proteins are members of the ATP binding cassette (ABC) superfamily of proteins. Binding and hydrolysis of MgATP at the SUR nucleotide binding domains (NBDs) lead to channel opening. Pancreatic KATP channels play an important role in insulin secretion. SUR1 mutations that result in increased levels of channel opening ultimately inhibit insulin secretion and lead to neonatal diabetes...
May 9, 2017: Biochemistry
https://www.readbyqxmd.com/read/28322929/exogenous-h2s-prevents-high-glucose-induced-damage-to-osteoblasts-through-regulation-of-katp-channels
#20
Yuanyuan Liu, Jianyong Liu, Xin Li, Fantao Wang, Xin Xu, Chunling Wang
Association between diabetes and osteoporosis has been extensively investigated. However, whether the effects of H2S on osteoblast function under high glucose (HG) condition relate to ATP-sensitive potassium (KATP) channels is unclear. This study aimed to investigate the effects of H2S on the proliferation, apoptosis, and mineralization of osteoblasts under HG condition, and observe whether H2S exert this effect through the KATP channels. Primary osteoblasts (POBs) were obtained from the calvaria of Sprague-Dawley rats...
June 2017: Biochimie
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