{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T07:02:09Z","timestamp":1773212529011,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T00:00:00Z","timestamp":1383004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL\/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of 500\u20132000. Mice given an HFD with BDSW showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that BDSW improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that BDSW recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, \u03b2-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with BDSW. BDSW increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. BDSW stimulated  phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that BDSW has potential as an  anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake.<\/jats:p>","DOI":"10.3390\/md11114193","type":"journal-article","created":{"date-parts":[[2013,10,29]],"date-time":"2013-10-29T15:39:00Z","timestamp":1383061140000},"page":"4193-4212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Anti-Diabetic Effect of Balanced Deep-Sea Water and Its Mode of Action in High-Fat Diet Induced Diabetic Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Byung","family":"Ha","sequence":"first","affiliation":[{"name":"Bio-Medical Research Institute, Kyungpook National University Hospital, 50 Samduk 2ga Jung-gu, Daegu 700-721, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun","family":"Shin","sequence":"additional","affiliation":[{"name":"Bio-Medical Research Institute, Kyungpook National University Hospital, 50 Samduk 2ga Jung-gu, Daegu 700-721, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung-Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Bio-Medical Research Institute, Kyungpook National University Hospital, 50 Samduk 2ga Jung-gu, Daegu 700-721, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Shon","sequence":"additional","affiliation":[{"name":"Bio-Medical Research Institute, Kyungpook National University Hospital, 50 Samduk 2ga Jung-gu, Daegu 700-721, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2013,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.pharmthera.2009.11.001","article-title":"Glycaemic control in type 2 diabetes: Targets and new therapies","volume":"125","author":"Tahrani","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nature11808","article-title":"Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP","volume":"494","author":"Miller","year":"2013","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.ijcard.2011.08.072","article-title":"Rosiglitazone induces arrhythmogenesis in diabetic hypertensive rats with calcium handling alteration","volume":"165","author":"Lee","year":"2011","journal-title":"Int. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/414821a","article-title":"New drug targets for type 2 diabetes and the metabolic syndrome","volume":"414","author":"Moller","year":"2001","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.bbagrm.2010.06.004","article-title":"Small molecules from natural sources, targeting signaling pathways in diabetes","volume":"1799","author":"Liu","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1248\/bpb.26.1552","article-title":"Pharmacological activity of deep-sea water: Examination of hyperlipemia prevention and medical treatment effect","volume":"26","author":"Yoshioka","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1248\/bpb.31.38","article-title":"Deep-sea water improves cardiovascular hemodynamics in Kurosawa and Kusanagi-Hypercholesterolemic (KHC) rabbits","volume":"31","author":"Katsuda","year":"2008","journal-title":"Biol. Pharm. Bull."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.3390\/md11062183","article-title":"Deep sea water modulates blood pressure and exhibits hypolipidemic effects via the AMPK-ACC pathway: An in vivo study","volume":"11","author":"Sheu","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_9","first-page":"83","article-title":"Improvement of skin symptoms and mineral imbalance by drinking deep sea water in patients with atopic eczema\/dermatitis syndrome (AEDS)","volume":"45","author":"Kimata","year":"2002","journal-title":"Acta Medica"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/sj.ejcn.1602218","article-title":"Drinking deep-sea water restores mineral imbalance in atopic eczema\/dermatitis syndrome","volume":"59","author":"Hataguchi","year":"2005","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1248\/bpb.27.1784","article-title":"Difference between deep seawater and surface seawater in the preventive effect of atherosclerosis","volume":"27","author":"Miyamura","year":"2004","journal-title":"Biol. Pharm. Bull."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1016\/0002-9343(92)90290-R","article-title":"Cellular calcium and manesium metabolism in the pathophysiology and treatment of hypertension and related metabolic disorders","volume":"93","author":"Resnick","year":"1992","journal-title":"Am. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.mehy.2005.09.006","article-title":"Magnesium or calcium hypophosphite could be a treatment for obesity in humans","volume":"66","author":"Robertson","year":"2006","journal-title":"Med. Hypotheses"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.clnu.2006.03.003","article-title":"Magnesium and diabetes mellitus: their relation","volume":"25","author":"Sales","year":"2006","journal-title":"Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s10126-008-9171-0","article-title":"Anti-obesity and antidiabetic effects of deep sea water on ob\/ob mice","volume":"11","author":"Hwang","year":"2009","journal-title":"Mar. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s10126-008-9131-8","article-title":"Inhibitory effect of deep-sea water on differentiation of 3T3-L1 adipocytes","volume":"11","author":"Hwang","year":"2009","journal-title":"Mar. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.bbrc.2009.06.073","article-title":"Intake of dissolved organic matter from deep seawater inhibits atherosclerosis progression","volume":"387","author":"Radhakrishnan","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1089\/jmf.2011.2007","article-title":"Drinking deep seawater decreases serum total and low-density lipoprotein-cholesterol in hypercholesterolemic subjects","volume":"15","author":"Fu","year":"2012","journal-title":"J. Med. Food"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/oby.2008.651","article-title":"Prevention of weight gain in adult patients with type 2 diabetes treated with pioglitazone","volume":"17","author":"Kushner","year":"2009","journal-title":"Obesity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.jnutbio.2012.03.004","article-title":"The role of dietary fatty acids in the pathology of metabolic syndrome","volume":"23","author":"Lottenberg","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3389\/fendo.2013.00071","article-title":"Adipokines mediate inflammation and insulin resistance","volume":"4","author":"Kwon","year":"2013","journal-title":"Front. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1042\/CS20050182","article-title":"Adiponectin: A key adipocytokine in metabolic syndrome","volume":"110","author":"Okamoto","year":"2006","journal-title":"Clin. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1210\/er.2005-0005","article-title":"Adiponectin and adiponectin receptors","volume":"26","author":"Kadowaki","year":"2005","journal-title":"Endocr. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1055\/s-2001-17297","article-title":"Rodent obesity models: an overview","volume":"109","author":"Tschop","year":"2001","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/sj.ijo.0801209","article-title":"Development of high fat diet-induced obesity and leptin resistance in C57Bl\/6J mice","volume":"24","author":"Lin","year":"2000","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cyto.2012.08.036","article-title":"Functional and structural features of adipokine family","volume":"61","author":"Raucci","year":"2013","journal-title":"Cytokine"},{"key":"ref_27","first-page":"4","article-title":"Recent advances in the relationship between obesity, inflammation, and insulin resistance","volume":"17","author":"Bastard","year":"2006","journal-title":"Eur. Cytokine Netw."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.3390\/nu4101367","article-title":"Differential development of glucose intolerance and pancreatic islet adaptation in multiple diet induced obesity models","volume":"4","author":"Omar","year":"2012","journal-title":"Nutrients"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/414799a","article-title":"Insulin signalling and the regulation of glucose and lipid metabolism","volume":"414","author":"Saltiel","year":"2001","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/nature07813","article-title":"AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity","volume":"458","author":"Canto","year":"2009","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3109\/07853890.2010.547211","article-title":"Sirtuin 1 in lipid metabolism and obesity","volume":"43","author":"Schug","year":"2011","journal-title":"Ann. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.biochi.2011.04.013","article-title":"Berberine acutely activates the glucose transport activity of GLUT1","volume":"93","author":"Cok","year":"2011","journal-title":"Biochimie"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1248\/bpb.33.1494","article-title":"7-O-methylaromadendrin stimulates glucose uptake and improves insulin resistance in vitro","volume":"33","author":"Zhang","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cmet.2007.03.006","article-title":"The GLUT4 glucose transporter","volume":"5","author":"Huang","year":"2007","journal-title":"Cell Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/physrev.00011.2008","article-title":"AMPK in Health and Disease","volume":"89","author":"Steinberg","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.cmet.2009.03.012","article-title":"AMPK: An emerging drug target for diabetes and the metabolic syndrome","volume":"9","author":"Zhang","year":"2009","journal-title":"Cell Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1073\/pnas.0308061100","article-title":"The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress","volume":"101","author":"Shaw","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"29060","DOI":"10.1074\/jbc.M503824200","article-title":"The Ca2+\/Calmodulin-dependent Protein Kinase Kinases Are AMP-activated Protein Kinase Kinases","volume":"280","author":"Hurley","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31880","DOI":"10.1074\/jbc.273.48.31880","article-title":"Components of a calmodulin-dependent protein kinase cascade. Molecular cloning, functional characterization and cellular localization of Ca2+\/calmodulin-dependent protein kinase kinase \u03b2","volume":"273","author":"Anderson","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.cmet.2008.02.011","article-title":"Hypothalamic CaMKK2 Contributes to the Regulation of Energy Balance","volume":"7","author":"Anderson","year":"2008","journal-title":"Cell Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.tibs.2005.11.009","article-title":"Chutes and Ladders: The search for protein kinases that act on AMPK","volume":"31","author":"Witters","year":"2006","journal-title":"Trends Biochem. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1039\/C0MB00089B","article-title":"Novel use of fluorescent glucose analogues to identify a new class of triazine-based insulin mimetics possessing useful secondary effects","volume":"2","author":"Jung","year":"2011","journal-title":"Mol. Biosyst."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/11\/11\/4193\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:50:14Z","timestamp":1760219414000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/11\/11\/4193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,29]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2013,11]]}},"alternative-id":["md11114193"],"URL":"https:\/\/doi.org\/10.3390\/md11114193","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10,29]]}}}