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https://www.readbyqxmd.com/read/29150777/glibenclamide-and-therapeutic-hypothermia-have-comparable-effect-on-attenuating-global-cerebral-edema-following-experimental-cardiac-arrest
#1
Shin Nakayama, Noriko Taguchi, Yumi Isaka, Takako Nakamura, Makoto Tanaka
BACKGROUND: Cerebral edema is one of the major causes of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). A subunit of the sulfonylurea receptor 1-transient receptor potential M4 (Sur1-TRPM4) channel has been implicated in the pathogenesis of ischemia-evoked cerebral edema. In this study, we examined whether glibenclamide (GBC), a Sur1-TRPM4 channel inhibitor, attenuates cerebral edema following CA/CPR and further examined the efficacy of GBC combined with therapeutic hypothermia...
November 17, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/29058186/methods-for-characterizing-disease-associated-atp-sensitive-potassium-channel-mutations
#2
Balamurugan Kandasamy, Show-Ling Shyng
The ATP-sensitive potassium (KATP) channel formed by the inwardly rectifying potassium channel Kir6.2 and the sulfonylurea receptor 1 (SUR1) plays a key role in regulating insulin secretion. Genetic mutations in KCNJ11 or ABCC8 which encode Kir6.2 and SUR1 respectively are major causes of insulin secretion disorders: those causing loss of channel function lead to congenital hyperinsulinism, whereas those causing gain of channel function result in neonatal diabetes and in some cases developmental delay, epilepsy, and neonatal diabetes, referred to as the DEND syndrome...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29054733/disrupted-ionic-homeostasis-in-ischemic-stroke-and-new-therapeutic-targets
#3
REVIEW
Hui-Jie Hu, Mingke Song
BACKGROUND: Stroke is a leading cause of long-term disability. All neuroprotectants targeting excitotoxicity have failed to become stroke medications. In order to explore and identify new therapeutic targets for stroke, we here reviewed present studies of ionic transporters and channels that are involved in ischemic brain damage. METHOD: We surveyed recent literature from animal experiments and clinical reports in the databases of PubMed and Elsevier ScienceDirect to analyze ionic mechanisms underlying ischemic cell damage and suggest promising ideas for stroke therapy...
October 17, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29048243/mithramycin-a-improves-functional-recovery-by-inhibiting-bscb-disruption-and-hemorrhage-after-spinal-cord-injury
#4
Jee Y Lee, Hae Y Choi, Chan S Park, Bong G Ju, Tae Y Yune
After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption and progressive hemorrhage lead to secondary injury, subsequent apoptosis and/or necrosis of neurons and glia, causing permanent neurological deficits. Growing evidence indicates that mithramycin A (MA), an anti-cancer drug, has neuroprotective effects in ischemic brain injury and Huntington's disease (HD). However, the precise mechanism underlying its protective effects is largely unknown. Here, we examined the effect of MA on BSCB breakdown and hemorrhage as well as subsequent inflammation after SCI...
November 17, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29035201/anti-diabetic-drug-binding-site-in-a-mammalian-katp-channel-revealed-by-cryo-em
#5
Gregory M Martin, Balamurugan Kandasamy, Frank DiMaio, Craig Yoshioka, Show-Ling Shyng
Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic KATP channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug glibenclamide and ATP at 3.63 Å resolution, which reveals unprecedented details of the ATP and glibenclamide binding sites...
October 24, 2017: ELife
https://www.readbyqxmd.com/read/28934129/a-comprehensive-survey-of-the-roles-of-highly-disordered-proteins-in-type-2-diabetes
#6
Zhihua Du, Vladimir N Uversky
Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with hyperglycemia (high blood sugar) related to either insulin resistance or insufficient insulin production. Among the various molecular events and players implicated in the manifestation and development of diabetes mellitus, proteins play several important roles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database has information on 34 human proteins experimentally shown to be related to the T2DM pathogenesis...
September 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28906027/sur1-trpm4-and-aqp4-form-a-heteromultimeric-complex-that-amplifies-ion-water-osmotic-coupling-and-drives-astrocyte-swelling
#7
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...
January 2018: Glia
https://www.readbyqxmd.com/read/28877214/direct-versus-indirect-actions-of-ghrelin-on-hypothalamic-npy-neurons
#8
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
#9
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
#10
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
#11
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
#12
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...
November 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28740332/a-protective-role-of-glibenclamide-in-inflammation-associated-injury
#13
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
#14
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. A d-LA-producing Saccharomyces cerevisiae strain JHY5610 is generated 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 lead 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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