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https://www.readbyqxmd.com/read/29792023/fern-9-11-ene-2%C3%AE-3%C3%AE-diol-action-on-insulin-secretion-in-hyperglycemic-conditions
#1
Allisson Jhonatan Gomes Castro, Luisa Helena Cazarolli, Gabrielle Da Luz, Delsi Altenhofen, Hemily Batista Da Silva, Francieli Kanumfre Carvalho, Moacir Geraldo Pizzolatti, Fátima Rmb Silva
The objective of this study was to investigate the effect and the mechanism of action of fernenediol as insulin secretagogue. Wistar rats were treated with 0.1; 1 and 10 mg/kg fernenediol and then induced hyperglycemia by oral glucose. The glycaemia, insulin, LDH, calcium and hepatic glycogen were analyzed. Considering the intestine and pancreas as targets for the triterpene action, the duodenum was used to verify the influence of fernenediol on intestinal glycosidases. Additionally, pancreatic islets were used for studies of 14 C-deoxyglucose uptake and influx of 45 Ca2+ in hyperglycemic medium with/without fernenediol in the presence/absence of an inhibitor/activator of KATP channels, glibenclamide, diazoxide, nifedipine, calcium chelator (BAPTA- AM) and H-89 and ST the inhibitors of the PKA and PKC enzymes...
May 24, 2018: Biochemistry
https://www.readbyqxmd.com/read/29773801/lrrc8-vrac-anion-channels-enhance-%C3%AE-cell-glucose-sensing-and-insulin-secretion
#2
Till Stuhlmann, Rosa Planells-Cases, Thomas J Jentsch
Glucose homeostasis depends critically on insulin that is secreted by pancreatic β-cells. Serum glucose, which is directly sensed by β-cells, stimulates depolarization- and Ca2+ -dependent exocytosis of insulin granules. Here we show that pancreatic islets prominently express LRRC8A and LRRC8D, subunits of volume-regulated VRAC anion channels. Hypotonicity- or glucose-induced β-cell swelling elicits canonical LRRC8A-dependent VRAC currents that depolarize β-cells to an extent that causes electrical excitation...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29772022/binding-of-sulphonylureas-to-plasma-proteins-a-katp-channel-perspective
#3
Peter Proks, Holger Kramer, Elizabeth Haythorne, Frances M Ashcroft
Sulphonylurea drugs stimulate insulin secretion from pancreatic β-cells primarily by inhibiting ATP sensitive potassium (KATP) channels in the β-cell membrane. The effective sulphonylurea concentration at its site of action is significantly attenuated by binding to serum albumin, which makes it difficult to compare in vitro and in vivo data. We therefore measured the ability of gliclazide and glibenclamide to inhibit KATP channels and stimulate insulin secretion in the presence of serum albumin. We used this data, together with estimates of free drug concentrations from binding studies, to predict the extent of sulphonylurea inhibition of KATP channels at therapeutic concentrations in vivo...
2018: PloS One
https://www.readbyqxmd.com/read/29768250/metabolic-regulation-of-synaptic-activity
#4
Sergei V Fedorovich, Tatyana V Waseem
Brain tissue is bioenergetically expensive. In humans, it composes approximately 2% of body weight and accounts for approximately 20% of calorie consumption. The brain consumes energy mostly for ion and neurotransmitter transport, a process that occurs primarily in synapses. Therefore, synapses are expensive for any living creature who has brain. In many brain diseases, synapses are damaged earlier than neurons start dying. Synapses may be considered as vulnerable sites on a neuron. Ischemic stroke, an acute disturbance of blood flow in the brain, is an example of a metabolic disease that affects synapses...
May 16, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29750770/genetic-characteristics-of-patients-with-congenital-hyperinsulinism
#5
Mary Ellen Vajravelu, Diva D De León
PURPOSE OF REVIEW: Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in infants and children. Early and appropriate recognition and treatment of hypoglycemia is vital to minimize neurocognitive impairment. RECENT FINDINGS: There are at least 11 known monogenic forms of hyperinsulinism and several associated syndromes. Molecular diagnosis allows for prediction of the effectiveness of diazoxide and the likelihood of focal hyperinsulinism...
May 9, 2018: Current Opinion in Pediatrics
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
#6
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/29736333/from-in-silico-to-in-vitro-a-trip-to-reveal-flavonoid-binding-on-the-rattus-norvegicus-kir6-1-atp-sensitive-inward-rectifier-potassium-channel
#7
Alfonso Trezza, Vittoria Cicaloni, Piera Porciatti, Andrea Langella, Fabio Fusi, Simona Saponara, Ottavia Spiga
Background: ATP-sensitive inward rectifier potassium channels (Kir), are a potassium channel family involved in many physiological processes. KATP dysfunctions are observed in several diseases such as hypoglycaemia, hyperinsulinemia, Prinzmetal angina-like symptoms, cardiovascular diseases. Methods: A broader view of the KATP mechanism is needed in order to operate on their regulation, and in this work we clarify the structure of the Rattus norvegicus ATP-sensitive inward rectifier potassium channel 8 (Kir6...
2018: PeerJ
https://www.readbyqxmd.com/read/29733479/levosimendan-differentially-modulates-electrophysiological-activities-of-sinoatrial-nodes-pulmonary-veins-and-the-left-and-right-atria
#8
Yung-Kuo Lin, Yao-Chang Chen, Yi-Ann Chen, Jen-Hung Huang, Shih-Ann Chen, Yi-Jen Chen
INTRODUCTION: Calcium overload increases the risk of atrial fibrillation (AF). Levosimedan, a calcium sensitizer, increases myofilament contractility. Clinical reports suggested that levosimendan might increase AF occurrence, but the electrophysiological effects of levosimendan on AF substrates and triggers (pulmonary veins, PVs) are not clear. METHODS AND RESULTS: Conventional microelectrodes were used to record action potentials (APs) in isolated rabbit PVs, sinoatrial nodes (SANs), the left atrium (LA), and right atrium (RA) before and after application of different concentrations of levosimendan with or without milrinone (a phosphodiesterase (PDE) III inhibitor) and glibenclamide (an ATP-sensitive potassium channel (KATP ) inhibitor)...
May 7, 2018: Journal of Cardiovascular Electrophysiology
https://www.readbyqxmd.com/read/29719445/mechanisms-involved-in-adenosine-pharmacological-preconditioning-induced-cardioprotection
#9
REVIEW
Lovedeep Singh, Ritu Kulshrestha, Nirmal Singh, Amteshwar Singh Jaggi
Adenosine is a naturally occurring breakdown product of adenosine triphosphate and plays an important role in different physiological and pathological conditions. Adenosine also serves as an important trigger in ischemic and remote preconditioning and its release may impart cardioprotection. Exogenous administration of adenosine in the form of adenosine preconditioning may also protect heart from ischemia-reperfusion injury. Endogenous release of adenosine during ischemic/remote preconditioning or exogenous adenosine during pharmacological preconditioning activates adenosine receptors to activate plethora of mechanisms, which either independently or in association with one another may confer cardioprotection during ischemia-reperfusion injury...
May 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29704592/cytoprotective-antioxidant-and-anti-inflammatory-mechanism-related-to-antiulcer-activity-of-cissampelos-sympodialis-eichl-in-animal-models
#10
Igor Rafael Praxedes De Sales, Rodrigo De Oliveira Formiga, Flávia Danniele Frota Machado, Raphaela Francelino Nascimento, Matheus Marley Bezerra Pessoa, Monique Emanuela Frutuoso Xavier Barros, Giciane Carvalho Vieira, Francisco Allysson Assis Ferreira Gadelha, Alexsandro Fernandes Marinho, José Maria Barbosa Filho, Raimundo Fernandes De Araújo Júnior, Aurigena Araújo Antunes, Leônia Maria Batista
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves and roots of Cissampelos sympodialis (Menispermaceae) are used by indian tribes and in folk medicine to treat genitourinary infections, inflammation, asthma and gastrointestinal disorders. MATERIAL AND METHODS: The standardized ethanolic extract (Cs-EtOHE) and alkaloids total fraction (Cs-TAF) obtained from aerial parts of C. sympodialis were evaluated in several models of acute gastric ulcers. The antisecretory and/or neutralizing mechanisms of the gastric acid secretion, cytoprotective, antioxidant and immunoregulatory mechanisms were also evaluated...
April 25, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29686622/inhibitory-neural-regulation-of-the-ca-2-transients-in-intramuscular-interstitial-cells-of-cajal-in-the-small-intestine
#11
Salah A Baker, Bernard T Drumm, Caroline A Cobine, Kathleen D Keef, Kenton M Sanders
Gastrointestinal motility is coordinated by enteric neurons. Both inhibitory and excitatory motor neurons innervate the syncytium consisting of smooth muscle cells (SMCs) interstitial cells of Cajal (ICC) and PDGFRα+ cells (SIP syncytium). Confocal imaging of mouse small intestines from animals expressing GCaMP3 in ICC were used to investigate inhibitory neural regulation of ICC in the deep muscular plexus (ICC-DMP). We hypothesized that Ca2+ signaling in ICC-DMP can be modulated by inhibitory enteric neural input...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29686518/mitochondria-from-rat-uterine-smooth-muscle-possess-atp-sensitive-potassium-channel
#12
Olga B Vadzyuk, Serhiy O Kosterin
The objective of this study was to detect ATP-sensitive K+ uptake in rat uterine smooth muscle mitochondria and to determine possible effects of its activation on mitochondrial physiology. By means of fluorescent technique with usage of K+ -sensitive fluorescent probe PBFI (potassium-binding benzofuran isophthalate) we showed that accumulation of K ions in isolated mitochondria from rat myometrium is sensitive to effectors of KATP -channel (ATP-sensitive K+ -channel) - ATP, diazoxide, glibenclamide and 5HD (5-hydroxydecanoate)...
March 2018: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/29685928/cryo-electron-microscopy-structures-and-progress-toward-a-dynamic-understanding-of-k-atp-channels
#13
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/29684589/hydrogen-sulfide-donor-nahs-stimulates-anp-secretion-via-the-k-atp-channel-and-the-nos-sgc-pathway-in-rat-atria
#14
Lamei Yu, Byung Mun Park, Yong Jin Ahn, Gi-Ja Lee, Suhn Hee Kim
Hydrogen sulfide (H2 S) is normally produced from L-cysteine in mammalian tissues and related to the pathogenesis of cardiovascular diseases. The aim of this study is to investigate the effects of H2 S donor on atrial natriuretic peptide (ANP) secretion and define its mechanism using normal and isoproterenol (ISP)-treated rats. Several H2 S donors were perfused into isolated beating rat atria, and atrial pressure (AP) and ANP secretion were measured. NaHS augmented high stretch-induced ANP secretion and decreased AP in a dose-dependent manner...
April 20, 2018: Peptides
https://www.readbyqxmd.com/read/29678572/sildenafil-protects-neuronal-cells-from-mitochondrial-toxicity-induced-by-%C3%AE-amyloid-peptide-via-atp-sensitive-k-channels
#15
Yonghae Son, Koanhoi Kim, Hyok-Rae Cho
To understand the molecular mechanisms underlying the beneficial effects of sildenafil in animal models of neurological disorders, we investigated the effects of sildenafil on the mitochondrial toxicity induced by β-amyloid (Aβ) peptide. Treatment of HT-22 hippocampal neuronal cells with Aβ25∼35 results in increased mitochondrial Ca2+ load, which is subsequently suppressed by sildenafil as well as by diazoxide, a selective opener of the ATP-sensitive K+ channels (KATP ). However, the suppressive effects of sildenafil and diazoxide are significantly attenuated by 5-hydroxydecanoic acid (5-HD), a KATP inhibitor...
April 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29675256/a-case-with-relapsed-transient-neonatal-diabetes-mellitus-treated-with-sulfonylurea-ending-chronic-insulin-requirement
#16
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/29671418/the-role-of-k-atp-channels-in-cerebral-ischemic-stroke-and-diabetes
#17
REVIEW
Vivian Szeto, Nai-Hong Chen, Hong-Shuo Sun, Zhong-Ping Feng
ATP-sensitive potassium (KATP ) channels are ubiquitously expressed on the plasma membrane of cells in multiple organs, including the heart, pancreas and brain. KATP channels play important roles in controlling and regulating cellular functions in response to metabolic state, which are inhibited by ATP and activated by Mg-ADP, allowing the cell to couple cellular metabolic state (ATP/ADP ratio) to electrical activity of the cell membrane. KATP channels mediate insulin secretion in pancreatic islet beta cells, and controlling vascular tone...
April 19, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29669221/role-of-ion-channels-in-the-functional-response-of-conjunctival-goblet-cells-to-dry-eye
#18
Donald G Puro
Optimal vision requires an ocular surface with a stable tear film whose many critical tasks include providing >70% of the eye's refractive power. However for millions, tear film instability produces uncomfortable sight-impairing dry eye. Despite the multitude of etiologies for dry eye, a universal hallmark is hyperosmolarity of the tear film. Presently, knowledge of how the ocular surface responds to hyperosmolarity remains incomplete with little understood about the role of ion channels. This bioelectric analysis focused on conjunctival goblet cells whose release of tear-stabilizing mucin is a key adaptive response to dry eye...
April 18, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29666184/atp-sensitive-potassium-channels-in-the-sinoatrial-node-contribute-to-heart-rate-control-and-adaptation-to-hypoxia
#19
Qadeer Aziz, Malcolm Finlay, David Montaigne, Leona Ojake, Yiwen Li, Naomi Anderson, Andreas Ludwig, Andrew Tinker
ATP-sensitive potassium channels (KATP ) contribute to membrane currents in many tissues, are responsive to intracellular metabolism, and open as ATP falls and ADP rises. KATP channels are widely distributed in tissues and are prominently expressed in the heart. They have generally been observed in ventricular tissue, but they are also expressed in the atria and conduction tissues. In this study, we focused on the contribution and role of the inwardly rectifying KATP channel subunit, Kir6.1, in the sinoatrial node (SAN)...
April 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29653089/modification-of-levosimendan-induced-suppression-of-atrial-natriuretic-peptide-secretion-in-hypertrophied-rat-atria
#20
Lamei Yu, Kuichang Yuan, Byung Mun Park, Suhn Hee Kim
This study aimed to determine the effects of levosimendan, a calcium sensitizer, on atrial contractility and atrial natriuretic peptide (ANP) secretion and its modification in hypertrophied atria. Isolated perfused beating rat atria were used from control and isoproterenol-treated rats. Levosimendan and its metabolite OR-1896 caused a positive inotropic effect and suppressed ANP secretion in rat atria. Similar to levosimendan, the selective phosphodiesterase 3 (PDE3) or PDE4 inhibitor also suppressed ANP secretion...
April 10, 2018: European Journal of Pharmacology
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