{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T21:39:57Z","timestamp":1761946797326,"version":"build-2065373602"},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,4,21]],"date-time":"2017-04-21T00:00:00Z","timestamp":1492732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Diabetes UK RD Lawrence Fellowship","award":["13\/0004647 to C. B"],"award-info":[{"award-number":["13\/0004647 to C. B"]}]},{"DOI":"10.13039\/100014669","name":"British Society for Neuroendocrinology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014669","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000382","name":"Society for Endocrinology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000382","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Mary Kinross Charitable Trust"},{"name":"Tenovus Scotland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2017,7]]},"abstract":"\n Aim<\/jats:title>\n \n To test the hypothesis that, given the role of\n AMP<\/jats:styled-content>\n \u2010activated protein kinase (\n AMPK<\/jats:styled-content>\n ) in regulating intracellular\n ATP<\/jats:styled-content>\n levels,\n AMPK<\/jats:styled-content>\n may alter\n ATP<\/jats:styled-content>\n release from astrocytes, the main sources of extracellular\n ATP<\/jats:styled-content>\n (\n eATP<\/jats:styled-content>\n ) within the brain.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n Measurements of\n ATP<\/jats:styled-content>\n release were made from human\n U373<\/jats:styled-content>\n astrocytoma cells, primary mouse hypothalamic (\n HTAS<\/jats:styled-content>\n ) and cortical astrocytes (\n CRTAS<\/jats:styled-content>\n ) and wild\u2010type and\n AMPK<\/jats:styled-content>\n \u03b11\/\u03b12 null mouse embryonic fibroblasts (\n MEFs<\/jats:styled-content>\n ). Cells were treated with drugs known to modulate\n AMPK<\/jats:styled-content>\n activity:\n A<\/jats:styled-content>\n \u2010769662,\n AICAR<\/jats:styled-content>\n and metformin, for up to 3\u2009hours. Intracellular calcium was measured using\n F<\/jats:styled-content>\n luo4 and\n F<\/jats:styled-content>\n ura\u20102 calcium\u2010sensitive fluorescent dyes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In\n U373<\/jats:styled-content>\n cells,\n A<\/jats:styled-content>\n \u2010769662 (100\u2009\u03bcM) increased\n AMPK<\/jats:styled-content>\n phosphorylation, whereas\n AICAR<\/jats:styled-content>\n and metformin (1\u2009mM) induced a modest increase or had no effect, respectively. Only\n A<\/jats:styled-content>\n \u2010769662 increased\n eATP<\/jats:styled-content>\n levels, and this was partially blocked by\n AMPK<\/jats:styled-content>\n inhibitor\n C<\/jats:styled-content>\n ompound\n C<\/jats:styled-content>\n . A\u2010769662\u2010induced increases in\n eATP<\/jats:styled-content>\n were preserved in\n AMPK<\/jats:styled-content>\n \u03b11\/\u03b12 null\n MEF<\/jats:styled-content>\n cells. A\u2010769662 increased intracellular calcium in\n U373<\/jats:styled-content>\n ,\n HTAS<\/jats:styled-content>\n and\n CRTAS<\/jats:styled-content>\n cells and chelation of intracellular calcium using\n BAPTA\u2010AM<\/jats:styled-content>\n reduced\n A<\/jats:styled-content>\n \u2010769662\u2010induced\n eATP<\/jats:styled-content>\n levels. A\u2010769662 also increased\n ATP<\/jats:styled-content>\n release from a number of other central and peripheral endocrine cell types.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n AMPK<\/jats:styled-content>\n is required to maintain basal\n eATP<\/jats:styled-content>\n levels but is not required for\n A<\/jats:styled-content>\n \u2010769662\u2010induced increases in\n eATP<\/jats:styled-content>\n . A\u2010769662 (>50\u2009\u03bcM) enhanced intracellular calcium levels leading to\n ATP<\/jats:styled-content>\n release in an\n AMPK<\/jats:styled-content>\n and purinergic receptor independent pathway.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12912","type":"journal-article","created":{"date-parts":[[2017,2,17]],"date-time":"2017-02-17T07:02:50Z","timestamp":1487314970000},"page":"997-1005","source":"Crossref","is-referenced-by-count":23,"title":["AMP<\/scp>\n \u2010activated protein kinase (\n AMPK<\/scp>\n ) activator\n A<\/scp>\n \u2010769662 increases intracellular calcium and\n ATP<\/scp>\n release from astrocytes in an\n AMPK<\/scp>\n \u2010independent manner"],"prefix":"10.1111","volume":"19","author":[{"given":"Julia M.","family":"Vlachaki Walker","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Clinical Sciences University of Exeter Medical School Exeter UK"},{"name":"Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School, University of Dundee Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josephine L.","family":"Robb","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Sciences University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana M.","family":"Cruz","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Sciences University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amrinder","family":"Malhi","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Sciences University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul G.","family":"Weightman Potter","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Sciences University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael L. J.","family":"Ashford","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School, University of Dundee Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rory J.","family":"McCrimmon","sequence":"additional","affiliation":[{"name":"Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School, University of Dundee Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate L. J.","family":"Ellacott","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Sciences University of Exeter Medical School Exeter UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4263-0866","authenticated-orcid":false,"given":"Craig","family":"Beall","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Sciences University of Exeter Medical School Exeter UK"},{"name":"Division of Molecular and Clinical Medicine Ninewells Hospital and Medical School, University of Dundee Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,4,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160048"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)80292-2"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00929-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.273.6.E1107"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02440"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300557200"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-0837"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-012-9300-0"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.139.7.1635"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004282107"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59660"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23233"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.21248"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2014.10.001"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3579-15.2016"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.07.028"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3725"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.002"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.043"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(93)90141-2"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.12.021"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(88)90159-1"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10124"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.12.001"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209454200"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2008.10.005"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.034140"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.09.024"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190721"},{"key":"e_1_2_6_31_1","first-page":"1","article-title":"Purinergic 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