{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T23:19:55Z","timestamp":1781824795328,"version":"3.54.5"},"reference-count":89,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T00:00:00Z","timestamp":1588550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T00:00:00Z","timestamp":1588550400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T00:00:00Z","timestamp":1588550400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR071381"],"award-info":[{"award-number":["R01AR071381"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR072602"],"award-info":[{"award-number":["R01AR072602"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM111254"],"award-info":[{"award-number":["R01GM111254"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["S1055024707"],"award-info":[{"award-number":["S1055024707"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Most glucose is processed in muscle, for energy or glycogen stores. Malignant Hyperthermia Susceptibility (MHS) exemplifies muscle conditions that increase [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>cytosol<\/jats:sub>\n                    . 42% of MHS patients have hyperglycemia. We show that phosphorylated glycogen phosphorylase (GP\n                    <jats:italic>a<\/jats:italic>\n                    ), glycogen synthase (GS\n                    <jats:italic>a<\/jats:italic>\n                    ) \u2013 respectively activated and inactivated by phosphorylation \u2013 and their Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -dependent kinase (PhK), are elevated in microsomal extracts from MHS patients\u2019 muscle. Glycogen and glucose transporter GLUT4 are decreased. [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>cytosol<\/jats:sub>\n                    , increased to MHS levels, promoted GP phosphorylation. Imaging at ~100 nm resolution located GP\n                    <jats:italic>a<\/jats:italic>\n                    at sarcoplasmic reticulum (SR) junctional cisternae, and\n                    <jats:italic>apo<\/jats:italic>\n                    -GP at Z disk. MHS muscle therefore has a wide-ranging alteration in glucose metabolism: high [Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ]\n                    <jats:sub>cytosol<\/jats:sub>\n                    activates PhK, which inhibits GS, activates GP and moves it toward the SR, favoring glycogenolysis. The alterations probably cause these patients\u2019 hyperglycemia. For basic studies, MHS emerges as a variable stressor, which forces glucose pathways from the normal to the diseased range, thereby exposing novel metabolic links.\n                  <\/jats:p>","DOI":"10.7554\/elife.53999","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T08:01:42Z","timestamp":1588579302000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.53999","source":"Crossref","is-referenced-by-count":31,"title":["Intracellular calcium leak lowers glucose storage in human muscle, promoting hyperglycemia and diabetes"],"prefix":"10.7554","volume":"9","author":[{"given":"Eshwar R","family":"Tammineni","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, Rush University Medical Center, Chicago, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Kraeva","sequence":"additional","affiliation":[{"name":"Malignant Hyperthermia Investigation Unit (MHIU) of the University 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Anaesthesia & Pain Management, Toronto General Hospital, UHN, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7906-0302","authenticated-orcid":true,"given":"Amira","family":"Klip","sequence":"additional","affiliation":[{"name":"Cell Biology Program, The Hospital for Sick Children, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Riazi","sequence":"additional","affiliation":[{"name":"Malignant Hyperthermia Investigation Unit (MHIU) of the University Health Network (Canada), Toronto, Canada"},{"name":"Department of Anaesthesia & Pain Management, Toronto General Hospital, UHN, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0985-8997","authenticated-orcid":true,"given":"Eduardo","family":"Rios","sequence":"additional","affiliation":[{"name":"Department of Physiology 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