{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T03:57:21Z","timestamp":1773115041340,"version":"3.50.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"Neopharma Japan Co., Ltd"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetes Ther"],"published-print":{"date-parts":[[2023,2]]},"DOI":"10.1007\/s13300-022-01335-8","type":"journal-article","created":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T16:24:06Z","timestamp":1669307046000},"page":"447-459","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pilot Trial on the Effect of 5-Aminolevulinic Acid on Glucose Tolerance in Patients with Maternally Inherited Diabetes and Deafness"],"prefix":"10.1007","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4950-291X","authenticated-orcid":false,"given":"Yuta","family":"Nakamura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0671-2530","authenticated-orcid":false,"given":"Ai","family":"Haraguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3430-5796","authenticated-orcid":false,"given":"Ichiro","family":"Horie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Abiru","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"1335_CR1","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1126\/science.aac7516","volume":"349","author":"RN Lightowlers","year":"2015","unstructured":"Lightowlers RN, Taylor RW, Turnbull DM. Mutations causing mitochondrial disease: what is new and what challenges remain? Science. 2015;349:1494\u20139.","journal-title":"Science"},{"key":"1335_CR2","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1056\/NEJM199404073301403","volume":"330","author":"T Kadowaki","year":"1994","unstructured":"Kadowaki T, Kadowaki H, Mori Y, et\u00a0al. A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N Engl J Med. 1994;330:962\u20138.","journal-title":"N Engl J Med"},{"key":"1335_CR3","doi-asserted-by":"publisher","first-page":"721","DOI":"10.7326\/0003-4819-134-9_Part_1-200105010-00008","volume":"134","author":"PJ Guillausseau","year":"2001","unstructured":"Guillausseau PJ, Massin P, Dubois-LaForgue D, et\u00a0al. Maternally inherited diabetes and deafness: a multicenter study. Ann Intern Med. 2001;134:721\u20138.","journal-title":"Ann Intern Med"},{"key":"1335_CR4","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S0168-8227(02)00246-2","volume":"59","author":"S Suzuki","year":"2003","unstructured":"Suzuki S, Oka Y, Kadowaki T, et\u00a0al. Clinical features of diabetes mellitus with the mitochondrial DNA 3243 (A-G) mutation in Japanese: maternal inheritance and mitochondria-related complications. Diabetes Res Clin Pract. 2003;59:207\u201317.","journal-title":"Diabetes Res Clin Pract"},{"key":"1335_CR5","doi-asserted-by":"publisher","first-page":"374","DOI":"10.2337\/diabetes.47.3.374","volume":"47","author":"ED Kennedy","year":"1998","unstructured":"Kennedy ED, Maechler P, Wollheim CB. Effects of depletion of mitochondrial DNA in metabolism secretion coupling in INS-1 cells. Diabetes. 1998;47:374\u201380.","journal-title":"Diabetes"},{"key":"1335_CR6","doi-asserted-by":"publisher","first-page":"20300","DOI":"10.1074\/jbc.273.32.20300","volume":"273","author":"T Hayakawa","year":"1998","unstructured":"Hayakawa T, Noda M, Yasuda K, et\u00a0al. Ethidium bromide-induced inhibition of mitochondrial gene transcription suppresses glucose-stimulated insulin release in the mouse pancreatic beta-cell line betaHC9. J Biol Chem. 1998;273:20300\u20137.","journal-title":"J Biol Chem"},{"key":"1335_CR7","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1007\/s00125-007-0779-9","volume":"50","author":"RG Whittaker","year":"2007","unstructured":"Whittaker RG, Schaefer AM, McFarland R, et\u00a0al. Prevalence and progression of diabetes in mitochondrial disease. Diabetologia. 2007;50:2085\u20139.","journal-title":"Diabetologia"},{"key":"1335_CR8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40360-016-0108-3","volume":"18","author":"U Ota","year":"2017","unstructured":"Ota U, Hara T, Nakagawa H, et\u00a0al. 5-aminolevulinic acid combined with ferrous ion reduces adiposity and improves glucose tolerance in diet-induced obese mice via enhancing mitochondrial function. BMC Pharmacol Toxicol. 2017;18:7.","journal-title":"BMC Pharmacol Toxicol"},{"key":"1335_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189593","volume":"13","author":"S Saitoh","year":"2018","unstructured":"Saitoh S, Okano S, Nohara H, et\u00a0al. 5-aminolevulinic acid (ALA) deficiency causes impaired glucose tolerance and insulin resistance coincident with an attenuation of mitochondrial function in aged mice. PLoS ONE. 2018;13: e0189593.","journal-title":"PLoS ONE"},{"key":"1335_CR10","doi-asserted-by":"publisher","first-page":"4013","DOI":"10.1038\/s41598-017-03917-0","volume":"7","author":"C Fujii","year":"2017","unstructured":"Fujii C, Miyashita K, Mitsuishi M, et\u00a0al. Treatment of sarcopenia and glucose intolerance through mitochondrial activation by 5-aminolevulinic acid. Sci Rep. 2017;7:4013.","journal-title":"Sci Rep"},{"key":"1335_CR11","doi-asserted-by":"publisher","first-page":"10549","DOI":"10.1038\/s41598-019-46772-x","volume":"9","author":"M Shimura","year":"2019","unstructured":"Shimura M, Nozawa N, Ogawa-Tominaga M, et\u00a0al. Effects of 5-aminolevulinic acid and sodium ferrous citrate on fibroblasts from individuals with mitochondrial diseases. Sci Rep. 2019;9:10549.","journal-title":"Sci Rep"},{"key":"1335_CR12","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1111\/j.1752-8062.2012.00421.x","volume":"5","author":"BL Rodriguez","year":"2012","unstructured":"Rodriguez BL, Curb JD, Davis J, et\u00a0al. Use of the dietary supplement 5-aminiolevulinic acid (5-ALA) and its relationship with glucose levels and hemoglobin A1C among individuals with prediabetes. Clin Transl Sci. 2012;5:314\u201320.","journal-title":"Clin Transl Sci"},{"key":"1335_CR13","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1016\/j.nut.2013.02.008","volume":"29","author":"F Higashikawa","year":"2013","unstructured":"Higashikawa F, Noda M, Awaya T, et\u00a0al. 5-aminolevulinic acid, a precursor of heme, reduces both fasting and postprandial glucose levels in mildly hyperglycemic subjects. Nutrition. 2013;29:1030\u20136.","journal-title":"Nutrition"},{"key":"1335_CR14","doi-asserted-by":"publisher","first-page":"415","DOI":"10.31989\/ffhd.v4i9.151","volume":"4","author":"N Yamashita","year":"2014","unstructured":"Yamashita N, Watanabe A, Kondo H, et\u00a0al. Safety test of a supplement, 5-aminolevulinic acid phosphate with sodium ferrous citrate, in diabetic patients treated with oral hypoglycemic agents. Funct Foods Health Dis. 2014;4:415\u201328.","journal-title":"Funct Foods Health Dis"},{"key":"1335_CR15","doi-asserted-by":"publisher","first-page":"8294805","DOI":"10.1155\/2016\/8294805","volume":"2016","author":"F Al-Saber","year":"2016","unstructured":"Al-Saber F, Aldosari W, Alselaiti M, et\u00a0al. The safety and tolerability of 5-aminolevulinic acid phosphate with sodium ferrous citrate in patients with type 2 diabetes mellitus in Bahrain. J Diabetes Res. 2016;2016:8294805.","journal-title":"J Diabetes Res"},{"key":"1335_CR16","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000025100","volume":"100","author":"Y Nakamura","year":"2021","unstructured":"Nakamura Y, Haraguchi A, Shigeno R, et\u00a0al. A single-arm, open-label, intervention study to investigate the improvement of glucose tolerance after administration of the 5-aminolevulinic acid (5-ALA) in the patients with mitochondrial diabetes mellitus. Medicine (Baltimore). 2021;100: e25100.","journal-title":"Medicine (Baltimore)"},{"key":"1335_CR17","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.diabres.2005.10.005","volume":"72","author":"A Tura","year":"2006","unstructured":"Tura A, Kautzky-Willer A, Pacini G. Insulinogenic indices from insulin and C-peptide: comparison of beta-cell function from OGTT and IVGTT. Diabetes Res Clin Pract. 2006;72:298\u2013301.","journal-title":"Diabetes Res Clin Pract"},{"key":"1335_CR18","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.2337\/diacare.27.6.1487","volume":"27","author":"TM Wallace","year":"2004","unstructured":"Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27:1487\u201395.","journal-title":"Diabetes Care"},{"key":"1335_CR19","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","volume":"22","author":"M Matsuda","year":"1999","unstructured":"Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999;22:1462\u201370.","journal-title":"Diabetes Care"},{"key":"1335_CR20","doi-asserted-by":"publisher","first-page":"4341","DOI":"10.1210\/jc.2019-00549","volume":"104","author":"Y Yang","year":"2019","unstructured":"Yang Y, Wang M, Tong J, et\u00a0al. Impaired glucose-stimulated proinsulin secretion is an early marker of \u03b2-cell impairment before prediabetes stage. J Clin Endocrinol Metab. 2019;104:4341\u20136.","journal-title":"J Clin Endocrinol Metab"},{"key":"1335_CR21","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1007\/s001250051316","volume":"42","author":"T Asano","year":"1999","unstructured":"Asano T, Tsukuda K, Katagiri H, et\u00a0al. Clinical relevance of heteroplasmic concentration of mitochondrial A3243G mutation in leucocytes. Diabetologia. 1999;42:1439\u201340.","journal-title":"Diabetologia"},{"key":"1335_CR22","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1111\/j.1464-5491.2008.02359.x","volume":"25","author":"R Murphy","year":"2008","unstructured":"Murphy R, Turnbull DM, Walker M, et\u00a0al. Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A>G mitochondrial point mutation. Diabet Med. 2008;25:383\u201399.","journal-title":"Diabet Med"},{"key":"1335_CR23","doi-asserted-by":"publisher","first-page":"543","DOI":"10.2337\/db08-0981","volume":"58","author":"MM Lindroos","year":"2009","unstructured":"Lindroos MM, Majamaa K, Tura A, et\u00a0al. m.3243A>G mutation in mitochondrial DNA leads to decreased insulin sensitivity in skeletal muscle and to progressive beta-cell dysfunction. Diabetes. 2009;58:543\u20139.","journal-title":"Diabetes"},{"key":"1335_CR24","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1161\/CIRCRESAHA.107.165472","volume":"102","author":"JA Kim","year":"2008","unstructured":"Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res. 2008;102:401\u201314.","journal-title":"Circ Res"},{"key":"1335_CR25","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1007\/978-3-319-55330-6_25","volume":"982","author":"A Gonzalez-Franquesa","year":"2017","unstructured":"Gonzalez-Franquesa A, Patti ME. Insulin resistance and mitochondrial dysfunction. Adv Exp Med Biol. 2017;982:465\u2013520.","journal-title":"Adv Exp Med Biol"},{"key":"1335_CR26","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/S0168-8227(99)00086-8","volume":"46","author":"KS Park","year":"1999","unstructured":"Park KS, Song JH, Lee KU, et\u00a0al. Peripheral blood mitochondrial DNA content correlates with lipid oxidation rate during euglycemic clamps in healthy young men. Diabetes Res Clin Pract. 1999;46:149\u201354.","journal-title":"Diabetes Res Clin Pract"},{"key":"1335_CR27","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.2337\/db05-1187","volume":"55","author":"K Imoto","year":"2006","unstructured":"Imoto K, Kukidome D, Nishikawa T, et\u00a0al. Impact of mitochondrial reactive oxygen species and apoptosis signal-regulating kinase 1 on insulin signaling. Diabetes. 2006;55:1197\u2013204.","journal-title":"Diabetes"},{"key":"1335_CR28","doi-asserted-by":"publisher","first-page":"8768954","DOI":"10.1155\/2020\/8768954","volume":"2020","author":"H Yaribeygi","year":"2020","unstructured":"Yaribeygi H, Maleki M, Sathyapalan T, et\u00a0al. Molecular mechanisms by which imeglimin improves glucose homeostasis. J Diabetes Res. 2020;2020:8768954.","journal-title":"J Diabetes Res"},{"key":"1335_CR29","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1111\/dom.14277","volume":"23","author":"S Hallakou-Bozec","year":"2021","unstructured":"Hallakou-Bozec S, Vial G, Kergoat M, et\u00a0al. Mechanism of action of imeglimin: a novel therapeutic agent for type 2 diabetes. Diabetes Obes Metab. 2021;23:664\u201373.","journal-title":"Diabetes Obes Metab"},{"key":"1335_CR30","doi-asserted-by":"publisher","first-page":"2254","DOI":"10.2337\/db14-1220","volume":"64","author":"G Vial","year":"2015","unstructured":"Vial G, Chauvin MA, Bendridi N, et\u00a0al. Imeglimin normalizes glucose tolerance and insulin sensitivity and improves mitochondrial function in liver of a high-fat, high-sucrose diet mice model. Diabetes. 2015;64:2254\u201364.","journal-title":"Diabetes"},{"key":"1335_CR31","doi-asserted-by":"publisher","DOI":"10.1002\/edm2.211","volume":"4","author":"G Vial","year":"2021","unstructured":"Vial G, Lamarche F, Cottet-Rousselle C, et\u00a0al. The mechanism by which imeglimin inhibits gluconeogenesis in rat liver cells. Endocrinol Diabetes Metab. 2021;4: e00211.","journal-title":"Endocrinol Diabetes Metab"},{"key":"1335_CR32","doi-asserted-by":"crossref","unstructured":"Rehani PR, Iftikhar H, Nakajima M, et\u00a0al. Safety and mode of action of diabetes medications in comparison with 5-aminolevulinic acid (5-ALA). J Diabetes Res 2019; p. 4267357.","DOI":"10.1155\/2019\/4267357"}],"container-title":["Diabetes Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13300-022-01335-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13300-022-01335-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13300-022-01335-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T20:51:01Z","timestamp":1677012661000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13300-022-01335-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,22]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,2]]}},"alternative-id":["1335"],"URL":"https:\/\/doi.org\/10.1007\/s13300-022-01335-8","relation":{},"ISSN":["1869-6953","1869-6961"],"issn-type":[{"value":"1869-6953","type":"print"},{"value":"1869-6961","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,22]]},"assertion":[{"value":"7 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 October 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}