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https://www.readbyqxmd.com/read/29775232/mannosylinositol-phosphorylceramides-and-ergosterol-coodinately-maintain-cell-wall-integrity-in-the-yeast-saccharomyces-cerevisiae
#1
Seiya Tanaka, Motohiro Tani
In the yeast Saccharomyces cerevisiae, complex sphingolipids have three types of polar head group, and breakdown of the normal composition causes several cellular dysfunctions. Previously we found that loss of biosynthesis of mannosylinositol phosphorylceramide (MIPC) causes a defect in cell wall integrity. In this study, we screened for multicopy suppressor genes that rescue the defect in cell wall integrity in cells lacking MIPC synthases (Sur1 and Csh1), and found that the defect is partly suppressed by upregulation of ergosterol biosynthesis...
May 18, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29751319/molecular-modelling-and-synthesis-of-spiroimidazolidine-2-4-diones-with-dual-activities-as-hypoglycemic-agents-and-selective-inhibitors-of-aldose-reductase
#2
Manar G Salem, Yasmine M Abdel Aziz, Marwa Elewa, Hosam A Elshihawy, Mohamed M Said
Novel derivatives of spiroimidazolidinedione were synthesized and evaluated as hypoglycemic agents through binding to sulfonylurea receptor 1 (SUR1) in pancreatic beta-cells. Their selectivity index was calculated against both aldehyde reductase (ALR1) and aldose reductase (ALR2). Aldehyde reductase is a key enzyme in the polyol pathway that is involved in the etiology of the secondary diabetic complications. All structures were confirmed by microanalysis and by IR, 1 H NMR, 13 C NMR and EI-MS spectroscopy...
May 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29737232/kir6-2-the-pore-forming-subunit-of-atp-sensitive-k-channels-is-overexpressed-in-human-post-traumatic-brain-contusions
#3
Lidia Castro, Montoya Noelia, Marian Vidal-Jorge, David Sanchez-Ortiz, Dario Gándara, Elena Martínez-Saez, Marta Cicuendez, Maria A Poca, J Marc Simard, Juan Sahuquillo
Brain contusions (BCs) are one of the most frequent lesions in patients with moderate and severe traumatic brain injury (TBI). BCs increase their volume due to perilesional edema formation and/or hemorrhagic transformation. This may have deleterious consequences and its mechanisms are still poorly understood. We previously identified de novo upregulation SUR1, the regulatory subunit of KATP and other channels, in human BCs. Our aim here was to study the expression of the pore-forming subunit of KATP, Kir6.2, in human BCs, and identify its localization in different cell types...
May 8, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29716892/human-proislet-peptide-promotes-pancreatic-progenitor-cells-to-ameliorate-diabetes-via-foxo1-menin-mediated-epigenetic-regulation
#4
Zongzhe Jiang, Diwen Shi, Yifan Tu, Jingjing Tian, Wenjian Zhang, Bowen Xing, Jihua Wang, Suhuan Liu, Jinning Lou, Jan-Åke Gustafsson, Xianxin Hua, Xiaosong Ma
In this study, we investigated how human proislet peptide (HIP) regulates differentiation of human fetus-derived pancreatic progenitor cells (HFPPCs), and explored the potential link between HIP signaling and the menin pathway, a key pathway that regulates differentiation of pancreatic islets. Our data showed that HIP promoted expression of pro-islet transcription factors (TFs) including PDX-1, MAFA and NKX6.1 as well as other maturation markers of β-cells such as insulin, GLUT2, KIR6.2, SUR1 and VDCC. Moreover, HIP increased insulin content, and promoted the ability of HFPPCs to normalize the blood glucose in diabetic mice...
May 1, 2018: Diabetes
https://www.readbyqxmd.com/read/29685928/cryo-electron-microscopy-structures-and-progress-toward-a-dynamic-understanding-of-k-atp-channels
#5
REVIEW
Michael C Puljung
Adenosine triphosphate (ATP)-sensitive K+ (KATP ) channels are molecular sensors of cell metabolism. These hetero-octameric channels, comprising four inward rectifier K+ channel subunits (Kir6.1 or Kir6.2) and four sulfonylurea receptor (SUR1 or SUR2A/B) subunits, detect metabolic changes via three classes of intracellular adenine nucleotide (ATP/ADP) binding site. One site, located on the Kir subunit, causes inhibition of the channel when ATP or ADP is bound. The other two sites, located on the SUR subunit, excite the channel when bound to Mg nucleotides...
April 23, 2018: Journal of General Physiology
https://www.readbyqxmd.com/read/29675256/a-case-with-relapsed-transient-neonatal-diabetes-mellitus-treated-with-sulfonylurea-ending-chronic-insulin-requirement
#6
Akihiko Ando, Shoichiro Nagasaka, Shun Ishibashi
We report a case of a woman with diabetes mellitus caused by a genetic defect in ABCC8 -coding sulfonylurea receptor 1 (SUR1), a subunit of the ATP-sensitive potassium (KATP ) channel protein. She was diagnosed with diabetes at 7 days after birth. After intravenous insulin drip for 1 month, her hyperglycaemia remitted. At the age of 13 years, her diabetes relapsed, and after that she had been treated by intensive insulin therapy for 25 years with relatively poor glycaemic control. She was switched to oral sulfonylurea therapy and attained euglycaemia...
2018: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29648981/glibenclamide-produces-region-dependent-effects-on-cerebral-edema-in-a-combined-injury-model-of-traumatic-brain-injury-and-hemorrhagic-shock-in-mice
#7
Ruchira Jha, Bradley J Molyneaux, Travis C Jackson, Jessica Wallisch, Seo-Young Park, Samuel M Poloyac, Vincent A Vagni, Keri L Janesko-Feldman, Keito Hoshitsuki, Margaret Beth Minnigh, Patrick M Kochanek
Cerebral edema is critical to morbidity/mortality in TBI and is worsened by hypotension. Glibenclamide may reduce cerebral edema by inhibiting sulfonylurea receptor-1 (Sur1); its effect on diffuse cerebral edema exacerbated by hypotension/resuscitation is unknown. We aimed to determine if glibenclamide improves pericontusional and/or diffuse edema in controlled cortical impact (CCI, 5m/s, 1 mm-depth)+hemorrhagic shock (HS, 35 minutes), and compare its effects in CCI alone. C57/BL6 mice were divided into 5 groups (n=10/group): naïve, CCI+vehicle, CCI+glibenclamide, CCI+HS+vehicle, and CCI+HS+glibenclamide...
March 8, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29617457/sur1-trpm4-channel-activation-and-phasic-secretion-of-mmp-9-induced-by-tpa-in-brain-endothelial-cells
#8
Volodymyr Gerzanich, Min Seong Kwon, Seung Kyoon Woo, Alexander Ivanov, J Marc Simard
BACKGROUND: Hemorrhagic transformation is a major complication of ischemic stroke, is linked to matrix metalloproteinase-9 (MMP-9), and is exacerbated by tissue plasminogen activator (tPA). Cerebral ischemia/reperfusion is characterized by SUR1-TRPM4 (sulfonylurea receptor 1-transient receptor potential melastatin 4) channel upregulation in microvascular endothelium. In humans and rodents with cerebral ischemia/reperfusion (I/R), the SUR1 antagonist, glibenclamide, reduces hemorrhagic transformation and plasma MMP-9, but the mechanism is unknown...
2018: PloS One
https://www.readbyqxmd.com/read/29594720/ligand-binding-and-conformational-changes-of-sur1-subunit-in-pancreatic-atp-sensitive-potassium-channels
#9
Jing-Xiang Wu, Dian Ding, Mengmeng Wang, Yunlu Kang, Xin Zeng, Lei Chen
ATP-sensitive potassium channels (KATP ) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic KATP channels control insulin release and regulate metabolism at the whole body level. They are implicated in many metabolic disorders and diseases and are therefore important drug targets. Here, we present three structures of pancreatic KATP channels solved by cryo-electron microscopy (cryo-EM), at resolutions ranging from 4.1 to 4.5 Å. These structures depict the binding site of the antidiabetic drug glibenclamide, indicate how Kir6...
March 28, 2018: Protein & Cell
https://www.readbyqxmd.com/read/29527407/transient-neonatal-diabetes-mellitus-in-a-very-preterm-infant-due-to-abcc8-mutation
#10
Barbara Piccini, Caterina Coviello, Livia Drovandi, Artuso Rosangela, Francesca Monzali, Emilio Casalini, Sabrina Giglio, Sonia Toni, Carlo Dani
Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes occurring within 6 months from birth. NDM can be permanent or transient (TNDM). We report the case of a preterm infant with TNDM due to an ABCC8 mutation identified by next-generation sequencing. The pancreatic adenosine triphosphate (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. The patient was successfully managed with insulin lispro at a 1:100 dilution, drawn up in an insulin pen injector with a 4-mm needle...
January 2018: American Journal of Perinatology Reports
https://www.readbyqxmd.com/read/29473496/modulation-of-hepatic-mrp3-abcc3-by-xenobiotics-and-pathophysiological-conditions-role-in-drug-pharmacokinetics
#11
Carolina I Ghanem, Jose E Manautou
Liver transporters play an important role in the pharmacokinetics and disposition of pharmaceuticals, environmental contaminants, and endogenous compounds. Among them, the family of ATP-Binding Cassette (ABC) transporters is the most important due to its role in the transport of endo- and xenobiotics. The ABCC sub-family is the largest one, consisting of 13 members that include the cystic fibrosis conductance regulator (CFTR/ABCC7); the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) and the multidrug resistance-associated proteins (MRPs)...
February 21, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29432787/possible-involvement-of-monoamine-neurons-in-the-emotional-abnormality-in-kir6-2-deficient-mice
#12
Atsumi Saito, Kazuya Miyagawa, Hiroko Miyagishi, Kazuhiro Kurokawa, Akira Umeda, Yasumasa Okada, Minoru Tsuji, Hiroshi Takeda
ATP-sensitive potassium (KATP ) channels consist of two structurally different subunits: a pore-forming subunit of the Kir6.0-family (Kir6.1 or Kir6.2) and a regulatory sulfonylurea receptor subunit (SUR1, SUR2A or SUR2B). Although Kir6.2 is widely distributed in the brain, the mechanisms that underlie the impact of Kir6.2 on emotional behavior are not yet fully understood. To clarify the role of Kir6.2 in emotional behavior, in the present study, we investigated the behavioral characteristics of Kir6.2-knockout (Kir6...
May 1, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29380238/activating-adenosine-a1-receptor-accelerates-pc12-cell-injury-via-adora1-pkc-katp-pathway-after-intermittent-hypoxia-exposure
#13
Hong-Fang Mei, Neha Poonit, Yi-Chun Zhang, Chu-Yuan Ye, Hui-Lin Cai, Chen-Yi Yu, Yong-Hai Zhou, Bei-Bei Wu, Jun Cai, Xiao-Hong Cai
Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with the neurocognitive deficits as a result of the neuronal cell injury. Previous studies have shown that adenosine A1 receptor (ADORA1) played an important role against hypoxia exposure, such as controlling the metabolic recovery in rat hippocampal slices and increasing the resistance in the combined effects of hypoxia and hypercapnia. However, little is known about whether ADORA1 takes part in the course of neuronal cell injury after intermittent hypoxia exposure which was the main pathological characteristic of OSAHS...
January 29, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29379989/modulation-of-excitability-of-stellate-neurons-in-the-ventral-cochlear-nucleus-of-mice-by-atp-sensitive-potassium-channels
#14
Ramazan Bal, Gurkan Ozturk, Ebru Onalan Etem, Aydin Him, Nurattin Cengiz, Tuncay Kuloglu, Mehmet Tuzcu, Caner Yildirim, Ahmet Tektemur
Major voltage-activated ionic channels of stellate cells in the ventral part of cochlear nucleus (CN) were largely characterized previously. However, it is not known if these cells are equipped with other ion channels apart from the voltage-sensitive ones. In the current study, it was aimed to study subunit composition and function of ATP-sensitive potassium channels (KATP ) in stellate cells of the ventral cochlear nucleus. Subunits of KATP channels, Kir6.1, Kir6.2, SUR1, and SUR2, were expressed at the mRNA level and at the protein level in the mouse VCN tissue...
February 2018: Journal of Membrane Biology
https://www.readbyqxmd.com/read/29348175/glucose-regulates-mafa-transcription-factor-abundance-and-insulin-gene-expression-by-inhibiting-amp-activated-protein-kinase-in-pancreatic-%C3%AE-cells
#15
Ryo Iwaoka, Kohsuke Kataoka
Insulin mRNA expression in pancreatic islet β-cells is up-regulated by extracellular glucose concentration, but the underlying mechanism remains incompletely understood. MafA is a transcriptional activator specifically enriched in β-cells that binds to the insulin gene promoter. Its expression is transcriptionally and posttranscriptionally regulated by glucose. Moreover, AMP-activated protein kinase (AMPK), a regulator of cellular energy homeostasis, is inhibited by high glucose, and this inhibition is essential for the up-regulation of insulin gene expression and glucose-stimulated insulin secretion (GSIS)...
March 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29286281/molecular-structure-of-human-katp-in-complex-with-atp-and-adp
#16
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/29218453/energy-depletion-and-not-ros-formation-is-a-crucial-step-of-glucolipotoxicity-gltx-in-pancreatic-beta-cells
#17
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...
March 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29180017/role-of-osteopontin-and-its-regulation-in-pancreatic-islet
#18
Mengyin Cai, Pradeep Bompada, Albert Salehi, Juan R Acosta, Rashmi B Prasad, David Atac, Markku Laakso, Leif Groop, Yang De Marinis
Osteopontin (OPN) is involved in various physiological processes and also implicated in multiple pathological states. It has been suggested that OPN may have a role in type 2 diabetes (T2D) by protecting pancreatic islets and interaction with incretins. However, the regulation and function of OPN in islets, especially in humans, remains largely unexplored. In this study, we performed our investigations on both diabetic mouse model SUR1-E1506K+/+ and islets from human donors. We demonstrated that OPN protein, secretion and gene expression was elevated in the diabetic SUR1-E1506K+/+ islets...
January 1, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29150777/glibenclamide-and-therapeutic-hypothermia-have-comparable-effect-on-attenuating-global-cerebral-edema-following-experimental-cardiac-arrest
#19
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
#20
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
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