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https://www.readbyqxmd.com/read/29159021/mitochondrial-uncoupler-triclosan-induces-vasorelaxation-of-rat-arteries
#1
Xiyue Zhang, Xinzi Zhang, Yanqiu Zhang, Mingyu Liu, Jing Jin, Jie Yan, Xin Shen, Nan Hu, Deli Dong
Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca(2+)]i, mitochondrial reactive oxygen species (mitoROS), and mitochondrial membrane potential of smooth muscle cells (A10 cells) were measured using laser scanning confocal microscopy...
November 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29151084/formal-neurocognitive-testing-in-60-patients-with-congenital-hyperinsulinism
#2
Anja Ludwig, Simone Enke, Janine Heindorf, Susann Empting, Thomas Meissner, Klaus Mohnike
BACKGROUND: Congenital hyperinsulinism (CHI) is hallmarked by persistent hypoketotic hypoglycemia in infancy. In the majority of all patients, CHI is caused by mutations in the KATP channel genes ABCC8 and KCNJ11, but other genes in the insulin-regulatory pathway have also been described. Repeated episodes of hypoglycemia include an increased risk of seizures and intellectual disability. So far, controlled psychometric studies on cognitive, motor, speech, and social-emotional outcome of CHI patients are missing...
November 17, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/29151079/mechanisms-of-vasorelaxation-induced-by-total-flavonoids-of-euphorbia-humifusa-in-rat-aorta
#3
T T Wang, Z Q Zhou, S Wang, X W Ji, B Wu, L Y Sun, J F Wen, D G Kang, H S Lee, K W Cho, S N Jin
Euphorbia humifusa Willd. (EH), rich in flavonoids, has long been used for the treatment of bacillary dysentery and enteritis in China, and is known to have antioxidant, hypotensive and hypolipidemic properties. However, the vasorelaxant effect of total flavonoids of EH (TFEH) and action mechanisms are not clearly defined yet. The aim of the present study was to investigate the effects of TFEH on the vascular tension and its underlying mechanisms. Experiments were performed in rat thoracic aorta using the organ bath system...
August 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29141871/potential-approaches-to-prevent-hypoglycemia-associated-autonomic-failure
#4
REVIEW
Eric Lontchi-Yimagou, Jee Young You, Michelle Carey, Ilan Gabriely, Harry Shamoon, Meredith Hawkins
Clear health benefits are associated with intensive glucose control in type 1 diabetes mellitus (T1DM). However, maintaining near-normal glycemia remains an elusive goal for many patients, in large part owing to the risk of severe hypoglycemia. In fact, recurrent episodes of hypoglycemia lead to 'hypoglycemia-associated autonomic failure' (HAAF), characterized by defective counter-regulatory responses to hypoglycemia. Extensive studies to understand the mechanisms underlying HAAF have revealed multiple potential etiologies, suggesting various approaches to prevent the development of HAAF...
November 14, 2017: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
https://www.readbyqxmd.com/read/29133341/the-trafficking-protein-ehd2-positively-regulates-cardiac-sarcolemmal-katp-channel-surface-expression-role-in-cardioprotection
#5
Hua Qian Yang, Kundan Jana, Michael J Rindler, William A Coetzee
ATP-sensitive K(+) (KATP) channels uniquely link cellular energy metabolism to membrane excitability and are expressed in diverse cell types that range from the endocrine pancreas to neurons and smooth, skeletal, and cardiac muscle. A decrease in the surface expression of KATP channels has been linked to various disorders, including dysregulated insulin secretion, abnormal blood pressure, and impaired resistance to cardiac injury. In contrast, up-regulation of KATP channel surface expression may be protective, for example, by mediating the beneficial effect of ischemic preconditioning...
November 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29128812/pharmacological-evidence-for-the-involvement-of-adenosine-triphosphate-sensitive-potassium-channels-in-chloroquine-induced-itch-in-mice
#6
Sattar Ostadhadi, Arash Foroutan, Nazgol-Sadat Haddadi, Abbas Norouzi-Javidan, Majid Momeny, Ghazaleh Zarrinrad, Seyed Hamid Ghaffari, Ahmad-Reza Dehpour
BACKGROUND: Chloroquine (CQ) evokes itch in human and scratching behavior in rodents through a histamine-independent pathway. Chloroquine directly excites peripheral sensory neurons which convey itch signals to the central nervous system. It has been revealed that ATP-sensitive potassium channels (KATP channels) are important in regulating neuronal excitability. Thus, we aimed to investigate the involvement of KATP channels in CQ-induced itch which may also reveal a linkage between metabolic state of cells and itch...
June 3, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29127764/could-a-combination-of-heterozygous-abcc8-and-kcnj11-mutations-cause-congenital-hyperinsulinism
#7
Klara Rozenkova, Azizun Nessa, Barbora Obermannova, Lenka Elblova, Petra Dusatkova, Zdenek Sumnik, Jan Lebl, Khalid Hussain, Stepanka Pruhova
BACKGROUND: Congenital hyperinsulinism (CHI) is frequently caused by mutations in one of the KATP channel subunits encoded by the genes ABCC8 and KCNJ11. The effect of simultaneous mutations in both of these genes on the pancreatic β-cell function is not known and patients with CHI carrying both ABCC8 and KCNJ11 mutations have not yet been reported. We questioned if a combination of heterozygous mutations in the ABCC8 and KCNJ11 genes could also lead to β-cell dysfunction presenting as CHI...
November 11, 2017: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/29119680/nicorandil-regulates-the-macrophage-skewing-and-ameliorates-myofibroblasts-by-inhibition-of-rhoa-rho-kinase-signalling-in-infarcted-rats
#8
Tsung-Ming Lee, Shinn-Zong Lin, Nen-Chung Chang
We have demonstrated that ATP-sensitive potassium (KATP ) channel agonists attenuated fibrosis; however, the mechanism remained unclear. Since RhoA has been identified as a mediator of cardiac fibrosis, we sought to determine whether the anti-fibrotic effects of KATP channel agonists were mediated via regulating macrophage phenotype and fibroblast differentiation by a RhoA/RhoA-kinase-dependent pathway. Wistar male rats after induction of myocardial infarction were randomized to either vehicle, nicorandil, an antagonist of KATP channel glibenclamide, an antagonist of ROCK fasudil, or a combination of nicorandil and glibenclamide or fasudil and glibenclamide starting 24 hrs after infarction...
November 9, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29118285/-memantine-improves-cognitive-function-via-katp-channel-inhibition
#9
Shigeki Moriguchi, Kohji Fukunaga
No abstract text is available yet for this article.
2017: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/29106387/loss-of-mtorc1-signaling-alters-pancreatic-%C3%AE-cell-mass-and-impairs-glucagon-secretion
#10
Nadejda Bozadjieva, Manuel Blandino-Rosano, Jennifer Chase, Xiao-Qing Dai, Kelsey Cummings, Jennifer Gimeno, Danielle Dean, Alvin C Powers, George K Gittes, Markus A Rüegg, Michael N Hall, Patrick E MacDonald, Ernesto Bernal-Mizrachi
Glucagon plays a major role in the regulation of glucose homeostasis during fed and fasting states. However, the mechanisms responsible for the regulation of pancreatic α cell mass and function are not completely understood. In the current study, we identified mTOR complex 1 (mTORC1) as a major regulator of α cell mass and glucagon secretion. Using mice with tissue-specific deletion of the mTORC1 regulator Raptor in α cells (αRaptorKO), we showed that mTORC1 signaling is dispensable for α cell development, but essential for α cell maturation during the transition from a milk-based diet to a chow-based diet after weaning...
November 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29097155/the-mechanism-of-action-and-role-of-hydrogen-sulfide-in-the-control-of-vascular-tone
#11
REVIEW
Eleni Dongó, Gabriella Beliczai-Marosi, Ane Stensønes Dybvig, Levente Kiss
Our knowledge about hydrogen sulfide (H2S) significantly changed over the last two decades. Today it is considered as not only a toxic gas but also as a gasotransmitter with diverse roles in different physiological and pathophysiological processes. H2S has pleiotropic effects and its possible mechanisms of action involve (1) a reversible protein sulfhydration which can alter the function of the modified proteins similar to nitrosylation or phosphorylation; (2) direct antioxidant effects and (3) interaction with metalloproteins...
October 30, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29079420/characterization-of-minoxidil-hydroxypropyl-%C3%AE-cyclodextrin-inclusion-complex-in-aqueous-alginate-gel-useful-for-alopecia-management-efficacy-evaluation-in-male-rat
#12
Domenico Tricarico, Fatima Maqoud, Angela Curci, Giuliamaria Camerino, Nicola Zizzo, Nunzio Denora, Annalisa Cutrignelli, Valentino Laquintana, Antonio Lopalco, Flavia la Forgia, Sergio Fontana, Massimo Franco, Angela Lopedota
Solid inclusion complex between hydroxypropyl-β-cyclodextrin (HP-β-CD) and minoxidil (MXD) was prepared by freeze-drying and characterized by yield, drug loading and dissolution rate. Moreover, the complex was formulated as alginate gel (GEL HP-β-CD)/MXD 3.5% w/w). The efficacy of the novel GEL HP-β-CD)/MXD 3.5% w/w and of MXD 3.5% w/w ethanolic/propylene-glycol solution (MXD solution) were evaluated by monitoring the hair growth of dorsal skin 1-4 weeks after depilation followed by histological analysis and gene expression in skin biopsies in male rat...
October 24, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29058186/methods-for-characterizing-disease-associated-atp-sensitive-potassium-channel-mutations
#13
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/29058183/probing-subunits-interactions-in-katp-channels-using-photo-crosslinking-via-genetically-encoded-p-azido-l-phenylalanine
#14
Prasanna Devaraneni, Emily A Rex, Show-Ling Shyng
Potassium channels are multimeric protein complexes regulated by diverse physiological and pharmacological ligands. The key to understanding mechanisms of channel regulation is the ability to detect structural changes associated with ligand binding. While high-resolution structural methods such as X-ray crystallography and single-particle cryo-electron microscopy offer direct visualization of channel structures, these methods do have limitations and may not be suitable for the question of interest. In this chapter, we describe the use of a photo-cross-linker unnatural amino acid, p-azido-L-phenylalanine, to probe interactions between two proteins, the sulfonylurea receptor 1 and the inwardly rectifying potassium channel Kir6...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29058181/monitoring-changes-in-the-abundance-of-endogenously-expressed-atp-sensitive-potassium-katp-channels-in-the-plasma-membrane-using-surface-biotinylation
#15
Jing-Syuna Ruan, Pei-Chun Chen
The conductance of KATP channel activity can be regulated by gating and/or surface expression. Gating analysis is usually performed by electrophysiological recording. Analysis of surface KATP channel expression levels requires cell fractionation, protein separation, and quantification. Cell fractionation involves time-consuming high-speed centrifugation steps and skilled techniques for taking out specific layers. Moreover, contamination of intracellular membranes can confound results. Although commercial kits have been developed to make it easier for scientists, qualities of these kits vary which can give rise to variable results...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29052402/-effect-of-qibai-pingfei-capsule-medicated-serum-on-protein-expressions-of-katp-channel-in-pulmonary-arterial-smooth-muscle-cells-via-nitric-oxide
#16
Jie Zhu, Ze-Geng Li, Bao-Qin Wang, Xiang-Li Tong, Qing-He Peng
To investigate the ATP-sensitive potassium channel (KATP channel) protein expressions during different periods under hypoxia condition and explore the effect of Qibai Pingfei capsule medicated serum (hereinafter referred to as QBPF) on the correlation between the protein expressions of KATP channel and nitric oxide in rat pulmonary arterial smooth muscle cells(PASMCs). Qibai Pingfei capsules were given to SD rats via continuous gavage for 10 days to obtain QBPF. Primary rats PASMCs were cultured by the direct adherent culture method...
April 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29044608/nutrient-sensing-in-pancreatic-islets-lessons-from-congenital-hyperinsulinism-and-monogenic-diabetes
#17
REVIEW
Ming Lu, Changhong Li
Pancreatic beta cells sense changes in nutrients during the cycles of fasting and feeding and release insulin accordingly to maintain glucose homeostasis. Abnormal beta cell nutrient sensing resulting from gene mutations leads to hypoglycemia or diabetes. Glucokinase (GCK) plays a key role in beta cell glucose sensing. As one form of congenital hyperinsulinism (CHI), activating mutations of GCK result in a decreased threshold for glucose-stimulated insulin secretion and hypoglycemia. In contrast, inactivating mutations of GCK result in diabetes, including a mild form (MODY2) and a severe form (permanent neonatal diabetes mellitus (PNDM))...
October 16, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/29035201/anti-diabetic-drug-binding-site-in-a-mammalian-katp-channel-revealed-by-cryo-em
#18
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/29024691/mechanisms-involved-in-the-increased-sensitivity-of-the-rabbit-basilar-artery-to-atrial-natriuretic-peptide-in-diabetes
#19
Mikahela A López-Morales, José M Centeno, Teresa Jover-Mengual, Vannina G Marrachelli, María C Burguete, María Castelló-Ruiz, Alicia Aliena-Valero, Enrique Alborch, Germán Torregrosa, Juan B Salom, Francisco J Miranda
Atrial natriuretic peptide (ANP) is a vasodilator with significant regional differences and controversial effects in the cerebral circulation, a vascular bed particularly prone to diabetes-induced complications. The present study has investigated how alloxan-induced diabetes modifies the mechanisms involved in the response of the rabbit basilar artery to ANP. ANP (10(-12)-10(-7)M) relaxed precontracted basilar arteries, with higher potency in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal reduced ANP-induced relaxations...
October 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28977595/glucose-sensitive-cftr-suppresses-glucagon-secretion-by-potentiating-katp-channels-in-pancreatic-islet-%C3%AE-cells
#20
Wen Qing Huang, Jing Hui Guo, Xiao Hu Zhang, Mei Kuen Yu, Yiu Wa Chung, Ye Chun Ruan, Hsiao Chang Chan
The secretion of glucagon by islet α cells is normally suppressed by high blood glucose, but this suppressibility is impaired in patients with diabetes or cystic fibrosis (CF), a disease caused by mutations in the gene encoding CF transmembrane conductance regulator (CFTR), a cyclic adenosine monophosphate-activated Cl- channel. However, precisely how glucose regulates glucagon release remains controversial. Here we report that elevated glucagon secretion, together with increased glucose-induced membrane depolarization and Ca2+ response, is found in CFTR mutant (DF508) mice/islets compared with the wild-type...
October 1, 2017: Endocrinology
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