{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:09:51Z","timestamp":1787731791249,"version":"build-2784847793"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T00:00:00Z","timestamp":1537488000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A2B4003422"],"award-info":[{"award-number":["2017R1A2B4003422"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2018.01071","type":"journal-article","created":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T09:17:02Z","timestamp":1537521422000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":65,"title":["Cucurbitacin B Induces Hypoglycemic Effect in Diabetic Mice by Regulation of AMP-Activated Protein Kinase Alpha and Glucagon-Like Peptide-1 via Bitter Taste Receptor Signaling"],"prefix":"10.3389","volume":"9","author":[{"given":"Kang-Hoon","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Seung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Young","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Jin","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeung-Jin","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12005","DOI":"10.1074\/jbc.C300557200","article-title":"AMP-activated protein kinase plays a role in the control of food intake.","volume":"279","author":"Andersson","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1523\/JNEUROSCI.3248-12.2013","article-title":"The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands.","volume":"33","author":"Born","year":"2013","journal-title":"J. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1016\/S0092-8674(00)80706-0","article-title":"T2Rs function as bitter taste receptors.","volume":"100","author":"Chandrashekar","year":"2000","journal-title":"Cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1039\/b418841c","article-title":"Cucurbitacins and cucurbitane glycosides: structures and biological activities.","volume":"22","author":"Chen","year":"2005","journal-title":"Nat. Prod. Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s00125-010-1986-3","article-title":"New aspects of an old drug: metformin as a glucagon-like peptide 1 (GLP-1) enhancer and sensitiser.","volume":"54","author":"Cho","year":"2011","journal-title":"Diabetologia"},{"key":"B6","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/BF02899698","article-title":"NCI-H716 cells as a model for endocrine differentiation in colorectal cancer.","volume":"62","author":"de Bruine","year":"1992","journal-title":"Virchows Arch. B Cell Pathol. Incl. Mol. Pathol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/nm.3787","article-title":"Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats.","volume":"21","author":"Duca","year":"2015","journal-title":"Nat. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1146\/annurev-physiol-021115-105439","article-title":"Enteroendocrine cells: chemosensors in the intestinal epithelium.","volume":"78","author":"Gribble","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1210\/en.2013-1750","article-title":"AMPK in the small intestine in normal and pathophysiological conditions.","volume":"155","author":"Harmel","year":"2014","journal-title":"Endocrinology"},{"key":"B10","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s13273-018-0007-3","article-title":"Leptin is a dose-dependent marker of caloric restriction in adipose tissues located in different parts of the mouse body.","volume":"14","author":"Hong","year":"2018","journal-title":"Mol. Cell. Toxicol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1038\/15981","article-title":"Ggamma13 colocalizes with gustducin in taste receptor cells and mediates IP3 responses to bitter denatonium.","volume":"2","author":"Huang","year":"1999","journal-title":"Nat. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062309","article-title":"Activation of AMPK by bitter melon triterpenoids involves Camkkbeta.","volume":"8","author":"Iseli","year":"2013","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"15069","DOI":"10.1073\/pnas.0706890104","article-title":"Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1.","volume":"104","author":"Jang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B14","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s13273-017-0050-5","article-title":"Gamma irradiation-induced liver injury and its amelioration by red ginseng extract.","volume":"13","author":"Jang","year":"2017","journal-title":"Mol. Cell. Toxicol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.tem.2012.11.006","article-title":"Nutrient sensing in the gut: new roads to therapeutics?","volume":"24","author":"Janssen","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2094","DOI":"10.1073\/pnas.1011508108","article-title":"Bitter taste receptors and alpha-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying.","volume":"108","author":"Janssen","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B17","doi-asserted-by":"publisher","first-page":"E671","DOI":"10.1152\/ajpendo.00492.2002","article-title":"Glucagon and regulation of glucose metabolism.","volume":"284","author":"Jiang","year":"2003","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B18","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1530\/JME-16-0099","article-title":"AMPK-dependent regulation of GLP1 expression in L-like cells.","volume":"57","author":"Jiang","year":"2016","journal-title":"J. Mol. Endocrinol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s13273-016-0047-5","article-title":"Dendropanax morbifera l\u00e9veille extract ameliorates memory impairments and inflammatory responses in the hippocampus of streptozotocin-induced type 1 diabetic rats.","volume":"12","author":"Jung","year":"2016","journal-title":"Mol. Cell. Toxicol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cmet.2004.12.003","article-title":"AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism.","volume":"1","author":"Kahn","year":"2005","journal-title":"Cell Metab."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00654","article-title":"Farnesol has an anti-obesity effect in high-fat diet-induced obese mice and induces the development of beige adipocytes in human adipose tissue derived-mesenchymal stem cells.","volume":"8","author":"Kim","year":"","journal-title":"Front. Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1007\/s13206-016-0403-5","article-title":"Development of GLP-1 secretagogue using microarray in enteroendocrine L cells.","volume":"10","author":"Kim","year":"2016","journal-title":"Biochip J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/s13206-016-0301-x","article-title":"Isolated protein of Astragalus membranaceus acts as an allergen by binding human immunoglobulin e on human sera.","volume":"10","author":"Kim","year":"2016","journal-title":"Biochip J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s13273-017-0023-8","article-title":"Proteins derived from Prunus armeniaca kernel are possible to cause immunoglobulin E reactivity in human sera.","volume":"13","author":"Kim","year":"","journal-title":"Mol. Cell. Toxicol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1007\/s00125-014-3326-5","article-title":"Denatonium induces secretion of glucagon-like peptide-1 through activation of bitter taste receptor pathways.","volume":"57","author":"Kim","year":"","journal-title":"Diabetologia"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/171742","article-title":"Medicinal plants qua glucagon-like peptide-1 secretagogue via intestinal nutrient sensors.","volume":"2015","author":"Kim","year":"2015","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/srep18325","article-title":"The aglycone of ginsenoside Rg3 enables glucagon-like peptide-1 secretion in enteroendocrine cells and alleviates hyperglycemia in type 2 diabetic mice.","volume":"5","author":"Kim","year":"2015","journal-title":"Sci. Rep."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14086-5","article-title":"Activation of intestinal olfactory receptor stimulates glucagon-like peptide-1 secretion in enteroendocrine cells and attenuates hyperglycemia in type 2 diabetic mice.","volume":"7","author":"Kim","year":"","journal-title":"Sci. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1530\/JOE-13-0381","article-title":"Metformin enhances glucagon-like peptide 1 via cooperation between insulin and Wnt signaling.","volume":"220","author":"Kim","year":"","journal-title":"J. Endocrinol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1124\/pr.108.000604","article-title":"The role of incretins in glucose homeostasis and diabetes treatment.","volume":"60","author":"Kim","year":"2008","journal-title":"Pharmacol. Rev."},{"key":"B31","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1111\/j.1748-1716.2011.02308.x","article-title":"Taste receptor signalling - from tongues to lungs.","volume":"204","author":"Kinnamon","year":"2012","journal-title":"Acta Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.tem.2006.05.006","article-title":"Expanding role of Ampk in endocrinology.","volume":"17","author":"Kola","year":"2006","journal-title":"Trends Endocrinol. Metab."},{"key":"B33","doi-asserted-by":"publisher","first-page":"25196","DOI":"10.1074\/jbc.C500175200","article-title":"Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase.","volume":"280","author":"Kola","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s00125-010-1929-z","article-title":"AMP-activated protein kinase regulates glucagon secretion from mouse pancreatic alpha cells.","volume":"54","author":"Leclerc","year":"2011","journal-title":"Diabetologia"},{"key":"B35","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s13273-017-0043-4","article-title":"Heterogeneous expression of Chlamydia pneumoniae antigen candidates and high-level soluble expression of its inclusion membrane proteins in Escherichia coli.","volume":"13","author":"Lee","year":"2017","journal-title":"Mol. Cell. Toxicol."},{"key":"B36","first-page":"S70","article-title":"Glucagon-like peptide 1 secretion by the L-cell.","volume":"55","author":"Lim","year":"2006","journal-title":"View From Within"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1074\/jbc.R100054200","article-title":"Molecular mechanisms of bitter and sweet taste transduction.","volume":"277","author":"Margolskee","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B38","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1093\/chemse\/bjp092","article-title":"The molecular receptive ranges of human Tas2R bitter taste receptors.","volume":"35","author":"Meyerhof","year":"2010","journal-title":"Chem. Senses"},{"key":"B39","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.cofs.2018.02.003","article-title":"Bioactive profile of pumpkin: an overview on terpenoids and their health-promoting properties.","volume":"22","author":"Montesano","year":"2018","journal-title":"Curr. Opin. Food Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"4610","DOI":"10.1210\/en.2011-1485","article-title":"Mechanisms underlying metformin-induced secretion of glucagon-like peptide-1 from the intestinal L cell.","volume":"152","author":"Mulherin","year":"2011","journal-title":"Endocrinology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1271\/bbb1961.52.1791","article-title":"Bitterness and structure relationship of the Triterpenoids from Ganoderma lucidum (Reishi).","volume":"52","author":"Nishitoba","year":"1988","journal-title":"Agric. Biol. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1111\/j.1476-5381.2009.00194.x","article-title":"The role of the PDE4D CAMP phosphodiesterase in the regulation of glucagon-like peptide-1 release.","volume":"157","author":"Ong","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s13273-017-0047-0","article-title":"The effect of purple rice (Oryza sativa L. indica) extract on the inflammatory response in a colon cancer cell line and dextran sulfate-induced tumor promotion in the rat colon.","volume":"13","author":"Phannasorn","year":"2017","journal-title":"Mol. Cell. Toxicol."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.7573\/dic.212283","article-title":"A clinical review of GLP-1 receptor agonists: efficacy and safety in diabetes and beyond.","volume":"4","author":"Prasad-Reddy","year":"2015","journal-title":"Drugs Context"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4522","DOI":"10.1210\/endo.142.10.8415","article-title":"A human cellular model for studying the regulation of glucagon-like peptide-1 secretion.","volume":"142","author":"Reimer","year":"2001","journal-title":"Endocrinology"},{"key":"B46","first-page":"1349","article-title":"Development of neuroendocrine tumors in the gastrointestinal tract of transgenic mice. Heterogeneity of hormone expression.","volume":"136","author":"Rindi","year":"1990","journal-title":"Am. J. Pathol."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149549","article-title":"Proglucagon promoter cre-mediated Ampk deletion in mice increases circulating Glp-1 levels and oral glucose tolerance.","volume":"11","author":"Sayers","year":"2016","journal-title":"PLoS One"},{"key":"B48","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1007\/BF00291980","article-title":"Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets.","volume":"28","author":"Schmidt","year":"1985","journal-title":"Diabetologia"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1177\/0960327112438289","article-title":"Coagulanolide modulates hepatic glucose metabolism in C57BL\/KsJ-db\/db mice.","volume":"31","author":"Singh","year":"2012","journal-title":"Hum. Exp. Toxicol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"5732","DOI":"10.1074\/jbc.M112.441477","article-title":"Emodin regulates glucose utilization by activating Amp-activated protein kinase.","volume":"288","author":"Song","year":"2013","journal-title":"J. Biol. Chem."},{"key":"B51","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jep.2015.06.042","article-title":"A bitter herbal medicine Gentiana scabra root extract stimulates glucagon-like peptide-1 secretion and regulates blood glucose in db\/db mouse.","volume":"172","author":"Suh","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.chembiol.2008.01.013","article-title":"Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the Ampk pathway.","volume":"15","author":"Tan","year":"2008","journal-title":"Chem. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1038\/381796a0","article-title":"Transduction of bitter and sweet taste by gustducin.","volume":"381","author":"Wong","year":"1996","journal-title":"Nature"},{"key":"B54","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1078\/0944-7113-00106","article-title":"Ginseng berry reduces blood glucose and body weight in db\/db mice.","volume":"9","author":"Xie","year":"2002","journal-title":"Phytomedicine"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2018.01071\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T09:17:06Z","timestamp":1537521426000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2018.01071\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,21]]},"references-count":54,"alternative-id":["10.3389\/fphar.2018.01071"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2018.01071","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.734199797.793552128","asserted-by":"object"}]},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,21]]},"article-number":"1071"}}