{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:15:23Z","timestamp":1782861323709,"version":"3.54.5"},"reference-count":64,"publisher":"Portland Press Ltd.","issue":"19","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The protein tyrosine kinase inhibitor imatinib is used in the treatment of various malignancies but may also promote beneficial effects in the treatment of diabetes. The aim of the present investigation was to characterize the mechanisms by which imatinib protects insulin producing cells. Treatment of non-obese diabetic (NOD) mice with imatinib resulted in increased beta-cell AMP-activated kinase (AMPK) phosphorylation. Imatinib activated AMPK also in vitro, resulting in decreased ribosomal protein S6 phosphorylation and protection against islet amyloid polypeptide (IAPP)-aggregation, thioredoxin interacting protein (TXNIP) up-regulation and beta-cell death. 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) mimicked and compound C counteracted the effect of imatinib on beta-cell survival. Imatinib-induced AMPK activation was preceded by reduced glucose\/pyruvate-dependent respiration, increased glycolysis rates, and a lowered ATP\/AMP ratio. Imatinib augmented the fractional oxidation of fatty acids\/malate, possibly via a direct interaction with the beta-oxidation enzyme enoyl coenzyme A hydratase, short chain, 1, mitochondrial (ECHS1). In non-beta cells, imatinib reduced respiratory chain complex I and II-mediated respiration and acyl-CoA carboxylase (ACC) phosphorylation, suggesting that mitochondrial effects of imatinib are not beta-cell specific. In conclusion, tyrosine kinase inhibitors modestly inhibit mitochondrial respiration, leading to AMPK activation and TXNIP down-regulation, which in turn protects against beta-cell death.<\/jats:p>","DOI":"10.1042\/cs20210604","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T13:41:57Z","timestamp":1632750117000},"page":"2243-2263","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Imatinib protects against human beta-cell death via inhibition of mitochondrial respiration and activation of AMPK"],"prefix":"10.1042","volume":"135","author":[{"given":"Andris","family":"Elksnis","sequence":"first","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas\u00a0A","family":"Schiffer","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Palm","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cen","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyril","family":"Turpaev","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"},{"name":"Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anongnad","family":"Ngamjariyawat","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shady","family":"Younis","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden"},{"name":"Division of Immunology and Rheumatology, Stanford University, Stanford, CA, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suling","family":"Huang","sequence":"additional","affiliation":[{"name":"State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Shen","sequence":"additional","affiliation":[{"name":"State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Leng","sequence":"additional","affiliation":[{"name":"State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bergsten","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Karlsborn","sequence":"additional","affiliation":[{"name":"Swedish Metabolomics Centre, KBC Byggnaden, Plan 3, Linnaeus v\u00e4g 6, 901 87 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5926-5407","authenticated-orcid":false,"given":"Nils","family":"Welsh","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2021,10,8]]},"reference":[{"key":"2021113011235627900_B1","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1056\/NEJMoa022457","article-title":"Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia","volume":"348","author":"O'Brien","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"2021113011235627900_B2","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1016\/S0959-8049(02)00836-5","article-title":"Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study","volume":"39","author":"Verweij","year":"2003","journal-title":"Eur. J. Cancer"},{"key":"2021113011235627900_B3","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1100\/tsw.2009.28","article-title":"Potential of small molecule protein tyrosine kinase inhibitors as immuno-modulators and inhibitors of the development of type 1 diabetes","volume":"9","author":"Little","year":"2009","journal-title":"Sci. World J."},{"key":"2021113011235627900_B4","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1042\/CS20090348","article-title":"Potential utility of small tyrosine kinase inhibitors in the treatment of diabetes","volume":"118","author":"Mokhtari","year":"2009","journal-title":"Clin. Sci. (Lond.)"},{"key":"2021113011235627900_B5","doi-asserted-by":"publisher","first-page":"4653","DOI":"10.1200\/JCO.2004.04.217","article-title":"Imatinib mesylate may improve fasting blood glucose in diabetic Ph+ chronic myelogenous leukemia patients responsive to treatment","volume":"22","author":"Breccia","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"2021113011235627900_B6","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1007\/s00277-012-1493-3","article-title":"Fasting glucose level reduction induced by imatinib in chronic myeloproliferative disease with TEL-PDGFRbeta rearrangement and type 1 diabetes","volume":"91","author":"Salaroli","year":"2012","journal-title":"Ann. Hematol."},{"key":"2021113011235627900_B7","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1096\/fj.06-6910com","article-title":"Amelioration of diabetes by imatinib mesylate (Gleevec): role of beta-cell NF-kappaB activation and anti-apoptotic preconditioning","volume":"21","author":"Hagerkvist","year":"2007","journal-title":"FASEB J."},{"key":"2021113011235627900_B8","doi-asserted-by":"publisher","first-page":"18895","DOI":"10.1073\/pnas.0810246105","article-title":"Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice","volume":"105","author":"Louvet","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2021113011235627900_B9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1042\/CS20070122","article-title":"Imatinib mesylate improves insulin sensitivity and glucose disposal rates in rats fed a high-fat diet","volume":"114","author":"Hagerkvist","year":"2008","journal-title":"Clin. Sci. (Lond.)"},{"key":"2021113011235627900_B10","doi-asserted-by":"publisher","first-page":"329","DOI":"10.2337\/db08-0080","article-title":"Imatinib mesylate reduces endoplasmic reticulum stress and induces remission of diabetes in db\/db mice","volume":"58","author":"Han","year":"2009","journal-title":"Diabetes"},{"key":"2021113011235627900_B11","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1016\/S2213-8587(21)00139-X","article-title":"Imatinib therapy for patients with recent-onset type 1 diabetes: a multicentre, randomized, double-blind, placebo-controlled, phase 2 trial","volume":"9","author":"Gitelman","year":"2021","journal-title":"Lancet Diab. Endocrinol."},{"key":"2021113011235627900_B12","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.yexcr.2006.10.011","article-title":"Consequences of Shb and c-Abl interactions for cell death in response to various stress stimuli","volume":"313","author":"Hagerkvist","year":"2006","journal-title":"Exp. Cell. Res."},{"key":"2021113011235627900_B13","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1016\/j.cellbi.2006.08.006","article-title":"Imatinib mesylate (Gleevec) protects against streptozotocin-induced diabetes and islet cell death in vitro","volume":"30","author":"Hagerkvist","year":"2006","journal-title":"Cell Biol. Int."},{"key":"2021113011235627900_B14","doi-asserted-by":"publisher","first-page":"07","DOI":"10.1016\/j.cmet.2017.04.026","article-title":"Targeting ABL-IRE1alpha Signaling Spares ER-Stressed Pancreatic beta Cells to Reverse Autoimmune Diabetes","volume":"25","author":"Morita","year":"2017","journal-title":"Cell Metab."},{"key":"2021113011235627900_B15","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1111\/dom.12152","article-title":"beta-Cell inflammation in human type 2 diabetes and the role of autophagy","volume":"3","author":"Marselli","year":"2013","journal-title":"Diabetes Obes. Metab."},{"key":"2021113011235627900_B16","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1042\/CS20130560","article-title":"Imatinib mesylate stimulates low-density lipoprotein receptor-related protein 1-mediated ERK phosphorylation in insulin-producing cells","volume":"128","author":"Fred","year":"2015","journal-title":"Clin. Sci. (Lond.)"},{"key":"2021113011235627900_B17","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1007\/s00125-013-2868-2","article-title":"Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells: role of Src homology 2-containing inositol 5'-phosphatase interaction with c-Abl","volume":"56","author":"Mokhtari","year":"2013","journal-title":"Diabetologia"},{"key":"2021113011235627900_B18","doi-asserted-by":"publisher","first-page":"e24831","DOI":"10.1371\/journal.pone.0024831","article-title":"Effects of Imatinib Mesylate (Gleevec) on human islet NF-kappaB activation and chemokine production in vitro","volume":"6","author":"Mokhtari","year":"2011","journal-title":"PLoS ONE"},{"key":"2021113011235627900_B19","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/978-3-319-43589-3_3","article-title":"AMPK regulation of cell growth, apoptosis, autophagy, and bioenergetics","volume":"107","author":"Villanueva-Paz","year":"2016","journal-title":"Exp. Suppl."},{"key":"2021113011235627900_B20","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.7150\/ijbs.12108","article-title":"AICAR and metformin exert AMPK-dependent effects on INS-1E pancreatic beta-cell apoptosis via differential downstream mechanisms","volume":"11","author":"Dai","year":"2015","journal-title":"Int. J. Biol. Sci."},{"key":"2021113011235627900_B21","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.mce.2015.07.015","article-title":"Role of the AMP kinase in cytokine-induced human EndoC-betaH1 cell death","volume":"414","author":"Fred","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"2021113011235627900_B22","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1213\/ANE.0000000000002385","article-title":"Isoflurane preconditioning alleviated murine liver ischemia and reperfusion injury by restoring AMPK\/mTOR-mediated autophagy","volume":"125","author":"Rao","year":"2017","journal-title":"Anesth. Analg."},{"key":"2021113011235627900_B23","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1111\/jnc.13922","article-title":"Cortical spreading depression preconditioning mediates neuroprotection against ischemic stroke by inducing AMP-activated protein kinase-dependent autophagy in a rat cerebral ischemic\/reperfusion injury model","volume":"140","author":"Shen","year":"2017","journal-title":"J. Neurochem."},{"key":"2021113011235627900_B24","doi-asserted-by":"publisher","first-page":"F731","DOI":"10.1152\/ajprenal.00541.2015","article-title":"Preconditioning mice with activators of AMPK ameliorates ischemic acute kidney injury in vivo","volume":"311","author":"Lieberthal","year":"2016","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"2021113011235627900_B25","doi-asserted-by":"publisher","first-page":"3589","DOI":"10.1172\/JCI58447","article-title":"A genetically engineered human pancreatic beta cell line exhibiting glucose-inducible insulin secretion","volume":"121","author":"Ravassard","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2021113011235627900_B26","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.ab.2004.04.037","article-title":"Design of experiments: an efficient strategy to identify factors influencing extraction and derivatization of Arabidopsis thaliana samples in metabolomic studies with gas chromatography\/mass spectrometry","volume":"331","author":"Gullberg","year":"2004","journal-title":"Anal. Biochem."},{"key":"2021113011235627900_B27","doi-asserted-by":"publisher","first-page":"8086","DOI":"10.1021\/ac051211v","article-title":"Extraction and GC\/MS analysis of the human blood plasma metabolome","volume":"77","author":"Aa","year":"2005","journal-title":"Anal. Chem."},{"key":"2021113011235627900_B28","doi-asserted-by":"publisher","first-page":"5635","DOI":"10.1021\/ac050601e","article-title":"High-throughput data analysis for detecting and identifying differences between samples in GC\/MS-based metabolomic analyses","volume":"77","author":"Jonsson","year":"2005","journal-title":"Anal. Chem."},{"key":"2021113011235627900_B29","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.febslet.2005.01.029","article-title":"GC-MS libraries for the rapid identification of metabolites in complex biological samples","volume":"579","author":"Schauer","year":"2005","journal-title":"FEBS Lett."},{"key":"2021113011235627900_B30","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1046\/j.1365-201X.1997.00222.x","article-title":"Rate of oxidative phosphorylation in isolated mitochondria from human skeletal muscle: effect of training status","volume":"161","author":"Tonkonogi","year":"1997","journal-title":"Acta Physiol. Scand."},{"key":"2021113011235627900_B31","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1136\/jmedgenet-2015-103231","article-title":"Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion","volume":"52","author":"Yamada","year":"2015","journal-title":"J. Med. Genet."},{"key":"2021113011235627900_B32","doi-asserted-by":"publisher","first-page":"3086","DOI":"10.1021\/jm070219p","article-title":"Discovery of potent, selective, orally bioavailable stearoyl-CoA desaturase 1 inhibitors","volume":"50","author":"Liu","year":"2007","journal-title":"J. Med. Chem."},{"key":"2021113011235627900_B33","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1096\/fj.201600835R","article-title":"ZBED6 negatively regulates insulin production, neuronal differentiation, and cell aggregation in MIN6 cells","volume":"33","author":"Wang","year":"2019","journal-title":"FASEB J."},{"key":"2021113011235627900_B34","doi-asserted-by":"publisher","first-page":"15997","DOI":"10.1073\/pnas.1303625110","article-title":"Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells","volume":"110","author":"Wang","year":"2013","journal-title":"PNAS"},{"key":"2021113011235627900_B35","doi-asserted-by":"publisher","first-page":"e20221","DOI":"10.1371\/journal.pone.0020221","article-title":"Drosophila melanogaster as a model system for studies of islet amyloid polypeptide aggregation","volume":"6","author":"Schultz","year":"2011","journal-title":"PLoS ONE"},{"key":"2021113011235627900_B36","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12986-016-0119-5","article-title":"Fatty acids stimulate insulin secretion from human pancreatic islets at fasting glucose concentrations via mitochondria-dependent and -independent mechanisms","volume":"13","author":"Cen","year":"2016","journal-title":"Nutrition Metab."},{"key":"2021113011235627900_B37","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/S0092-8674(00)80213-5","article-title":"The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor","volume":"89","author":"Brown","year":"1997","journal-title":"Cell"},{"key":"2021113011235627900_B38","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1152\/ajpendo.1999.277.1.E1","article-title":"AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes","volume":"277","author":"Winder","year":"1999","journal-title":"Am. J. Physiol."},{"key":"2021113011235627900_B39","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1007\/s00125-013-2991-0","article-title":"Molecular mechanism of action of metformin: old or new insights?","volume":"56","author":"Rena","year":"2013","journal-title":"Diabetologia"},{"key":"2021113011235627900_B40","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.bbrc.2003.07.019","article-title":"mTOR integrates amino acid- and energy-sensing pathways","volume":"313","author":"Tokunaga","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021113011235627900_B41","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1038\/nature08675","article-title":"Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors","volume":"463","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"2021113011235627900_B42","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1210\/me.2014-1095","article-title":"Minireview: Thioredoxin-interacting protein: regulation and function in the pancreatic beta-cell","volume":"28","author":"Shalev","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"2021113011235627900_B43","doi-asserted-by":"publisher","first-page":"e28804","DOI":"10.1371\/journal.pone.0028804","article-title":"AMP-activated protein kinase (AMPK) mediates nutrient regulation of thioredoxin-interacting protein (TXNIP) in pancreatic beta-cells","volume":"6","author":"Shaked","year":"2011","journal-title":"PLoS ONE"},{"key":"2021113011235627900_B44","doi-asserted-by":"publisher","first-page":"1469","DOI":"10.1007\/s00125-011-2366-3","article-title":"Arctigenin, a natural compound, activates AMP-activated protein kinase via inhibition of mitochondria complex I and ameliorates metabolic disorders in ob\/ob mice","volume":"55","author":"Huang","year":"2012","journal-title":"Diabetologia"},{"key":"2021113011235627900_B45","doi-asserted-by":"publisher","first-page":"2798269","DOI":"10.1155\/2016\/2798269","article-title":"Islet amyloid polypeptide: structure, function, and pathophysiology","author":"Akter","year":"2016","journal-title":"J. Diabetes Res."},{"key":"2021113011235627900_B46","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.cmet.2016.09.005","article-title":"Metformin targets central carbon metabolism and reveals mitochondrial requirements in human cancers","volume":"24","author":"Liu","year":"2016","journal-title":"Cell Metab."},{"key":"2021113011235627900_B47","doi-asserted-by":"publisher","first-page":"709","DOI":"10.2337\/db18-0557","article-title":"Absence of TXNIP in humans leads to lactic acidosis and low serum methionine linked to deficient respiration on pyruvate","volume":"68","author":"Katsu-Jimenez","year":"2019","journal-title":"Diabetes"},{"key":"2021113011235627900_B48","doi-asserted-by":"publisher","first-page":"e0120879","DOI":"10.1371\/journal.pone.0120879","article-title":"Characterization of stimulus-secretion coupling in the human pancreatic EndoC-\u03b2H1 beta cell line","volume":"10","author":"Andersson","year":"2015","journal-title":"PloS ONE"},{"key":"2021113011235627900_B49","doi-asserted-by":"publisher","first-page":"e0199505","DOI":"10.1371\/journal.pone.0199505","article-title":"Pro-inflammatory cytokines attenuate glucose-stimulated insulin secretion from INS-1E insulinoma cells by restricting mitochondrial pyruvate oxidation capacity - Novel mechanistic insight from real-time analysis of oxidative phosphorylation","volume":"13","author":"Barlow","year":"2018","journal-title":"PLoS ONE"},{"key":"2021113011235627900_B50","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1080\/15548627.2019.1695399","article-title":"The GID ubiquitin ligase complex is a regulator of AMPK activity and organismal lifespan","volume":"16","author":"Liu","year":"2020","journal-title":"Autophagy"},{"key":"2021113011235627900_B51","first-page":"77","article-title":"Clinical pharmacokinetics of imatinib mesylate","volume":"19","author":"Leveque","year":"2005","journal-title":"In Vivo"},{"key":"2021113011235627900_B52","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.chembiol.2017.05.021","article-title":"Mechanisms of Paradoxical Activation of AMPK by the Kinase Inhibitors SU6656 and Sorafenib","volume":"24","author":"Ross","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"2021113011235627900_B53","doi-asserted-by":"publisher","first-page":"29773","DOI":"10.1074\/jbc.M109.032144","article-title":"Structural basis for the mechanism of respiratory complex I","volume":"284","author":"Berrisford","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021113011235627900_B54","doi-asserted-by":"publisher","first-page":"288","DOI":"10.2203\/dose-response.13-035.Ristow","article-title":"Mitohormesis: promoting health and lifespan by increased levels of reactive oxygen species (ROS)","volume":"12","author":"Ristow","year":"2014","journal-title":"Dose Response"},{"key":"2021113011235627900_B55","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1016\/j.bcp.2008.09.004","article-title":"Possible role of an ischemic preconditioning-like response mechanism in K(ATP) channel opener-mediated protection against streptozotocin-induced suppression of rat pancreatic islet function","volume":"76","author":"Sandler","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"2021113011235627900_B56","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.3727\/096368912X658728","article-title":"A preexistent hypoxic gene signature predicts impaired islet graft function and glucose homeostasis","volume":"22","author":"Cantley","year":"2013","journal-title":"Cell Transplant."},{"key":"2021113011235627900_B57","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1471-230X-12-4","article-title":"High-dose clevudine impairs mitochondrial function and glucose-stimulated insulin secretion in INS-1E cells","volume":"12","author":"Jang","year":"2012","journal-title":"BMC Gastroenterol."},{"key":"2021113011235627900_B58","doi-asserted-by":"publisher","first-page":"63149","DOI":"10.1007\/s00125-019-05030-5","article-title":"Activation of the HIF1\u03b1\/PFKFB3 stress response pathway in beta cells in type 1 diabetes","author":"Nomoto","year":"2020","journal-title":"Diabetologia"},{"key":"2021113011235627900_B59","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1530\/JOE-19-0180","article-title":"microRNA-375 regulates glucose metabolism-related signaling for insulin secretion","volume":"244","author":"Dumortier","year":"2020","journal-title":"Endocrinol"},{"key":"2021113011235627900_B60","doi-asserted-by":"publisher","first-page":"3422","DOI":"10.1210\/endo.140.8.6908","article-title":"Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro","volume":"140","author":"Carlsson","year":"1999","journal-title":"Endocrinology"},{"key":"2021113011235627900_B61","doi-asserted-by":"publisher","first-page":"4154","DOI":"10.1210\/en.2003-0410","article-title":"Saturated fatty acids synergize with elevated glucose to cause pancreatic beta-cell death","volume":"144","author":"El-Assaad","year":"2003","journal-title":"Endocrinology"},{"key":"2021113011235627900_B62","first-page":"241","article-title":"AMPK activation: a therapeutic target for type 2 diabetes?","volume":"7","author":"Coughlan","year":"2014","journal-title":"Diab. Metab. Syndr. Obes."},{"key":"2021113011235627900_B63","doi-asserted-by":"publisher","first-page":"4934","DOI":"10.1038\/ncomms5934","article-title":"Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes","volume":"5","author":"Lim","year":"2014","journal-title":"Nat. Commun."},{"key":"2021113011235627900_B64","doi-asserted-by":"publisher","first-page":"e125317","DOI":"10.1172\/jci.insight.125317","article-title":"B lymphocytes protect islet \u03b2 cells in diabetes prone NOD mice treated with imatinib","volume":"5","author":"Wilson","year":"2019","journal-title":"JCI Insight"}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/135\/19\/2243\/921533\/cs-2021-0604.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/135\/19\/2243\/921533\/cs-2021-0604.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T12:19:30Z","timestamp":1638274770000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/135\/19\/2243\/229850\/Imatinib-protects-against-human-beta-cell-death"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":64,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2021,10,14]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20210604","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,10]]},"published":{"date-parts":[[2021,10]]}}}