{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:02:06Z","timestamp":1787061726440,"version":"build-2736575974"},"reference-count":29,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T00:00:00Z","timestamp":1626048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSC 98-2622-B-019-001-CC3"],"award-info":[{"award-number":["NSC 98-2622-B-019-001-CC3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Although the hypoglycemic potential of brewer\u2019s yeast extract has been reported, there is limited information pertaining to the hypoglycemic ingredients of Saccharomyces pastorianus extract and their mechanisms of action available. This study aimed to investigate the in vivo and in vitro hypoglycemic effect of S. pastorianus extract and to elucidate its molecular mechanisms. S. pastorianus extract was mainly composed of proteins followed by carbohydrates. In diabetic rats, oral administration of S. pastorianus extract significantly reduced the levels of plasma glucose and enhanced the activity of hepatic glucose-6-phosphatase dehydrogenase. Treatment with S. pastorianus extract increased the localization of type 4 glucose transporter (GLUT4), PTP, and insulin receptor at 3T3-L1 cell membranes and raised the levels of P38 MAPK, PI3K, and AKT in the cytosol. In agreement with these results, pretreatment of 3T3-L1 cells with inhibitors of PTP, PI3K, Akt\/PKB, and p38 MAPK inhibited glucose uptake induced by application of S. pastorianus extract. Most importantly, a 54 kDa protein with hypoglycemic activity was identified and suggested as the major ingredient contributing to the hypoglycemic activity of S. pastorianus extract. In summary, these results clearly confirm the hypoglycemic activity of S. pastorianus extract and provide critical insights into the underlying molecular mechanisms.<\/jats:p>","DOI":"10.3390\/molecules26144232","type":"journal-article","created":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T21:56:37Z","timestamp":1626126997000},"page":"4232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Exploration of Hypoglycemic Activity of Saccharomyces pastorianus Extract and Evaluation of the Molecular Mechanisms"],"prefix":"10.3390","volume":"26","author":[{"given":"Chien-Hui","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Seafood Science, National Kaohsiung University of Science and Technology, Nanzi 81157, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2295-6412","authenticated-orcid":false,"given":"Chung-Hsiung","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chuan","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Hsien","family":"Chang","sequence":"additional","affiliation":[{"name":"Institute of Food Safety and Risk Management, National Taiwan Ocean University, Keelung 20224, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Jane","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Taiwan Ocean University, Keelung 20224, Taiwan"},{"name":"Center for Marine Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,12]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"269","DOI":"10.5001\/omj.2012.68","article-title":"Type 2 diabetes mellitus: A review of current trends","volume":"27","author":"Olokoba","year":"2012","journal-title":"Oman Med. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"18677","DOI":"10.3390\/ijms151018677","article-title":"Molecular mechanisms for the regulation of insulin-stimulated glucose uptake by small guanosine triphosphatases in skeletal muscle and adipocytes","volume":"15","author":"Satoh","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0885-4505(89)90011-X","article-title":"The glucose-6-phosphatase\/glucokinase ratio in the liver of obese-diabetic subjects","volume":"41","author":"Belfiore","year":"1989","journal-title":"Biochem. Med. Metab. Biol."},{"key":"ref_5","first-page":"223","article-title":"Increased hexokinase\/glucose-6-phosphatase ratio in the diabetic kidney as index of glucose overutilization","volume":"7","author":"Belfiore","year":"1989","journal-title":"Clin. Physiol. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e58-e58","DOI":"10.2337\/dc11-2527","article-title":"Glucose-6-phosphate dehydrogenase deficiency and type 2 diabetes","volume":"35","author":"Heymann","year":"2012","journal-title":"Diabetes Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.2337\/dc15-0843","article-title":"Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium\u2013glucose cotransporter 2 inhibition","volume":"38","author":"Peters","year":"2015","journal-title":"Diabetes Care"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Osadebe, P.O., Odoh, E.U., and Uzor, P.F. (2014). Natural products as potential sources of antidiabetic drugs. J. Pharm. Res. Int., 2075\u20132095.","DOI":"10.9734\/BJPR\/2014\/8382"},{"key":"ref_9","first-page":"6773","article-title":"In vitro investigation of the hypoglycemic activity of yeasts using models of rat epididymal adipocyte and differentiated mouse 3T3-L1 adipocyte","volume":"10","author":"Wu","year":"2011","journal-title":"Afr. J. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jbiosc.2011.04.012","article-title":"Effects of cultural medium and conditions on the proliferation and hypoglycemic activity of Saccharomyces pastorianus no. 54","volume":"112","author":"Wu","year":"2011","journal-title":"J. Biosci. Bioeng."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.foodchem.2016.05.016","article-title":"Proximate composition, functional properties, amino acid, mineral and vitamin contents of a novel food: Alhydwan (Boerhavia elegana Choisy) seed flour","volume":"211","author":"Zhang","year":"2016","journal-title":"Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/0305-0491(87)90060-5","article-title":"Free imidazole compounds in white and dark muscles of migratory marine fish","volume":"87","author":"Suzuki","year":"1987","journal-title":"Comp. Biochem. Physiol. B"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.microc.2016.07.008","article-title":"Interference free and fast determination of manganese (II), iron (III) and copper (II) ions in different real samples by flame atomic absorption spectroscopy after column graphene oxide-based solid phase extraction","volume":"129","author":"Pourjavid","year":"2016","journal-title":"Microchem. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4745","DOI":"10.1016\/S0021-9258(19)85559-X","article-title":"Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes","volume":"255","author":"Student","year":"1980","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.yexcr.2004.08.030","article-title":"High extracellular calcium attenuates adipogenesis in 3T3-L1 preadipocytes","volume":"301","author":"Jensen","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_16","first-page":"661","article-title":"Effects of high and low molecular weight chitosan on plasma cholesterol, glucose and adipocytokines in diabetic rats induced by streptozotocin and nicotinamide","volume":"20","author":"Chang","year":"2012","journal-title":"J. Food Drug Anal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1016\/S0021-9258(19)76910-5","article-title":"Hepatic glucokinase in fed, fasted and alloxian-diabetic rats","volume":"235","author":"Dipietro","year":"1960","journal-title":"J. Biol. Chem."},{"key":"ref_18","first-page":"381","article-title":"Glucokinase methods enzymol","volume":"Volume 9","author":"Colowick","year":"1984","journal-title":"Methods Enzymol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0076-6879(55)01046-X","article-title":"Glucose-6-phosphate dehydrogenase","volume":"Volume 1","author":"Colowick","year":"1955","journal-title":"Methods Enzymol"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"589","DOI":"10.2331\/suisan.38.589","article-title":"Distribution of glucose-6-phosphate metabolizing enzyme in fish","volume":"38","author":"Nagayama","year":"1972","journal-title":"Nippon Suisan Gakk."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/elps.1150090603","article-title":"Improved staining of proteins in polyacrylamide gels including isoelectric focusing gels with clear background at nanogram sensitivity using Coomassie Brilliant Blue G-250 and R-250","volume":"9","author":"Neuhoff","year":"1988","journal-title":"Electrophoresis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.biopha.2018.06.076","article-title":"Effect of Monacolin K and COQ10 supplementation in hypertensive and hypercholesterolemic subjects with metabolic syndrome","volume":"105","author":"Mazza","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF02784584","article-title":"The isolation of glucose tolerance factors from brewer\u2019s yeast and their relation to chromium","volume":"32","author":"Simonoff","year":"1992","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S0271-5317(85)80241-4","article-title":"Dietary chromium and effect of chromium supplementation on glucose tolerance of elderly Canadian women","volume":"5","author":"Martinez","year":"1985","journal-title":"Nutr. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1111\/1750-3841.14138","article-title":"Antidiabetic effect of high-chromium yeast against type 2 diabetic KK-Ay Mice","volume":"83","author":"Liu","year":"2018","journal-title":"J. Food Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9665","DOI":"10.1021\/acs.jafc.7b03782","article-title":"Orally administered baker\u2019s yeast \u03b2-glucan promotes glucose and lipid homeostasis in the livers of obesity and diabetes model mice","volume":"65","author":"Cao","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Bengal, Y., Aviram, S., and Hayek, T. (2020). p38 MAPK in glucose metabolism of skeletal muscle: Beneficial or harmful?. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186480"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15771","DOI":"10.1016\/S0021-9258(18)98476-0","article-title":"The bisindolylmaleimide GF 109203X is a potent and selective inhibitor of protein kinase C","volume":"266","author":"Toullec","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.biopha.2018.02.084","article-title":"Investigation of insulin resistance in the popularly used four rat models of type-2 diabetes","volume":"101","author":"Chao","year":"2018","journal-title":"Biomed. Pharmacother."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/14\/4232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:29:27Z","timestamp":1760164167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/14\/4232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,12]]},"references-count":29,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["molecules26144232"],"URL":"https:\/\/doi.org\/10.3390\/molecules26144232","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,12]]}}}