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ATP sensitive potassium channel

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https://www.readbyqxmd.com/read/29773871/the-somatostatin-secreting-pancreatic-%C3%AE-cell-in-health-and-disease
#1
REVIEW
Patrik Rorsman, Mark O Huising
The somatostatin-secreting δ-cells comprise ~5% of the cells of the pancreatic islets. The δ-cells have complex morphology and might interact with many more islet cells than suggested by their low numbers. δ-Cells contain ATP-sensitive potassium channels, which open at low levels of glucose but close when glucose is elevated. This closure initiates membrane depolarization and electrical activity and increased somatostatin secretion. Factors released by neighbouring α-cells or β-cells amplify the glucose-induced effects on somatostatin secretion from δ-cells, which act locally within the islets as paracrine or autocrine inhibitors of insulin, glucagon and somatostatin secretion...
May 17, 2018: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/29772022/binding-of-sulphonylureas-to-plasma-proteins-a-katp-channel-perspective
#2
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/29750770/genetic-characteristics-of-patients-with-congenital-hyperinsulinism
#3
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/29747754/mechanism-of-resveratrol-induced-relaxation-of-the-guinea-pig-fundus
#4
Ching-Chung Tsai, Shu-Leei Tey, Ming-Che Lee, Ching-Wen Liu, Yu-Tsun Su, Shih-Che Huang
BACKGROUND: Resveratrol is a polyphenolic compound that can be isolated from plants and also is a constituent of red wine. Resveratrol induces relaxation of vascular smooth muscle and may prevent cardiovascular diseases. PURPOSE: Impaired gastric accommodation plays an important role in functional dyspepsia and fundic relaxation and is a therapeutic target of functional dyspepsia. Although drugs for fundic relaxation have been developed, these types of drugs are still rare...
April 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29746171/increased-task-channel-mediated-currents-underlie-high-fat-diet-induced-vagal-afferent-dysfunction
#5
Sung Jin Park, Yang Yu, Brittany Wagner, William C Valinsky, Alan E Lomax, Michael J Beyak
We have previously demonstrated that satiety sensing vagal afferent neurons are less responsive to meal-related stimuli in obesity, due to reduced electrical excitability. As leak K+ currents are key determinants of membrane excitability, we hypothesized that leak K+ currents are increased in vagal afferents during obesity. Diet-induced obesity (DIO) was induced by feeding C57Bl/6J mice a high fat fed diet (60% energy from fat - HFF) for 8-10 weeks. In vitro extracellular recordings were performed on jejunal afferent nerves...
May 10, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
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
#6
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
#7
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/29686743/antinociceptive-activity-of-methanolic-extract-of-clinacanthus-nutans-leaves-possible-mechanisms-of-action-involved
#8
Zainul Amiruddin Zakaria, Mohammad Hafiz Abdul Rahim, Rushduddin Al Jufri Roosli, Mohd Hijaz Mohd Sani, Maizatul Hasyima Omar, Siti Farah Mohd Tohid, Fezah Othman, Siew Mooi Ching, Arifah Abdul Kadir
Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. The antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes ( β -funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, α 2 -noradrenergic (yohimbine), β -adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride)...
2018: Pain Research & Management: the Journal of the Canadian Pain Society
https://www.readbyqxmd.com/read/29686518/mitochondria-from-rat-uterine-smooth-muscle-possess-atp-sensitive-potassium-channel
#9
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/29675256/a-case-with-relapsed-transient-neonatal-diabetes-mellitus-treated-with-sulfonylurea-ending-chronic-insulin-requirement
#10
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
#11
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/29670283/genetic-identification-of-leptin-neural-circuits-in-energy-and-glucose-homeostases
#12
Jie Xu, Christopher L Bartolome, Cho Shing Low, Xinchi Yi, Cheng-Hao Chien, Peng Wang, Dong Kong
Leptin, a hormone produced in white adipose tissue, acts in the brain to communicate fuel status, suppress appetite following a meal, promote energy expenditure and maintain blood glucose stability1,2 . Dysregulation of leptin or its receptors (LEPR) results in severe obesity and diabetes3-5 . Although intensive studies on leptin have transformed obesity and diabetes research2,6 , clinical applications of the molecule are still limited 7 , at least in part owing to the complexity and our incomplete understanding of the underlying neural circuits...
April 18, 2018: Nature
https://www.readbyqxmd.com/read/29666184/atp-sensitive-potassium-channels-in-the-sinoatrial-node-contribute-to-heart-rate-control-and-adaptation-to-hypoxia
#13
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/29651960/targeting-brain-tumors-with-nanomedicines-overcoming-challenges-of-blood-brain-barrier
#14
Nagendra S Ningaraj, Polluru L Reddy, Divya Khaitan
This review elucidates ongoing research, which show improved delivery of anticancer drugs alone and/ or enclosed in carriers collectively called nanomedicines to cross the Blood brain barrier (BBB) / blood-brain tumor barrier (BTB) to kill tumor cells and impact patient survival. We highlighted various advances in understanding the mechanism of BTB function that impact on anticancer therapeutics delivery. We discussed latest breakthroughs in developing pharmaceutical strategies, including nanomedicines and delivering them across BTB for brain tumor management and treatment...
April 12, 2018: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/29594720/ligand-binding-and-conformational-changes-of-sur1-subunit-in-pancreatic-atp-sensitive-potassium-channels
#15
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/29589989/a-unique-allosteric-insulin-receptor-monoclonal-antibody-that-prevents-hypoglycemia-in-the-sur-1-mouse-model-of-katp-hyperinsulinism
#16
Puja Patela, Lawrenshey Charles, John Corbin, Ira D Goldfine, Kirk Johnson, Paul Rubin, Diva D De León
Loss-of-function mutations of the ß-cell ATP-sensitive potassium channels (KATP ) cause the most common and severe form of congenital hyperinsulinism (KATP HI), a disorder of ß-cell function characterized by severe hypoglycemia. Children with KATP HI are typically unresponsive to medical therapy and require pancreatectomy for intractable hypoglycemia. We tested the hypothesis that inhibition of insulin receptor signaling may prevent hypoglycemia in KATP HI. To test this hypothesis, we examined the effect of an antibody allosteric inhibitor of the insulin receptor, XMetD, on fasting plasma glucose in a mouse model of KATP HI (SUR-1- / - mice)...
March 28, 2018: MAbs
https://www.readbyqxmd.com/read/29555329/anti-nociceptive-mechanisms-of-flavonoids-rich-methanolic-extract-from-terminalia-coriacea-roxb-wight-arn-leaves
#17
Mohammed Safwan Ali Khan, Nishat Ahmed, Misbah, Mohammed Arifuddin, Zainul Amiruddin Zakaria, Mohammad M Al-Sanea, Syeda Umme Kulsoom Khundmiri, Inshah Ahmed, Saleha Ahmed, Pooi Ling Mok
In view of the report on anti-nociceptive activity of Leathery Murdah, Terminalia coriacea {Roxb.} Wight & Arn. (Combretaceae) leaves, the present study was conducted to isolate the active constituents and identify the underlying mechanisms. The methanolic extract of T. coriacea leaves (TCLME) at doses 125, 250 and 500 mg/kg orally, was subjected to various in-vivo assays in acetic acid induced writhing and formalin induced paw-licking tests with aspirin (100 mg/kg) and morphine (5 mg/kg) as reference drugs...
May 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29543503/calcitonin-gene-related-peptide-hyperpolarizes-mouse-pulmonary-artery-endothelial-tubes-through-katp-channel-activation
#18
Charles E Norton, Steven S Segal
The sensory neurotransmitter calcitonin gene-related peptide (CGRP) is associated with vasodilation of systemic arteries through activation of ATP-sensitive potassium channels (KATP) in smooth muscle cells (SMCs), however its effects on endothelial cell (EC) membrane potential (Vm) are unresolved. In pulmonary arteries (PAs) of C57BL/6J mice, we questioned whether CGRP would hyperpolarize ECs as well as SMCs. Intact PAs were isolated and immunostained for CGRP to confirm sensory innervation; vessel segments (length, 1-2 mm; diameter ∼150 µm) with intact or denuded endothelium were cannulated and pressurized to 16 cm H2O at 37{degree sign}C...
March 15, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29540778/kir6-1-k-atp-channel-modulates-microglia-phenotypes-implication-in-parkinson-s-disease
#19
Ren-Hong Du, Hong-Bin Sun, Zhao-Li Hu, Ming Lu, Jian-Hua Ding, Gang Hu
Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson's disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6...
March 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29524844/hyperhomocysteinemia-potentiates-diabetes-impaired-edhf-induced-vascular-relaxation-role-of-insufficient-hydrogen-sulfide
#20
Zhongjian Cheng, Xinggui Shen, Xiaohua Jiang, Huimin Shan, Maria Cimini, Pu Fang, Yong Ji, Joon Young Park, Konstantinos Drosatos, Xiaofeng Yang, Christopher G Kevil, Raj Kishore, Hong Wang
Insufficient hydrogen sulfide (H2 S) has been implicated in Type 2 diabetic mellitus (T2DM) and hyperhomocysteinemia (HHcy)-related cardiovascular complications. We investigated the role of H2 S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA) of db/db mice fed a high methionine (HM) diet. HM diet (8 weeks) induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively), and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF)-induced endothelium-dependent relaxation to acetylcholine (ACh), determined by the presence of eNOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and prostacyclin (PGI2 ) inhibitor indomethacin (INDO), in SMA from db/db mice but not that from db/+ mice...
June 2018: Redox Biology
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