{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:32:42Z","timestamp":1790962362411,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T00:00:00Z","timestamp":1445299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The glucose-lowering effects of lupin seeds involve the combined action of several components. The present study investigates the influence of one of the main quinolizidine alkaloids, lupanine, on pancreatic beta cells and in an animal model of type-2 diabetes mellitus. In vitro studies were performed with insulin-secreting INS-1E cells or islets of C57BL\/6 mice. In the in vivo experiments, hyperglycemia was induced in rats by injecting streptozotocin (65 mg\/kg body weight). In the presence of 15 mmol\/L glucose, insulin secretion was significantly elevated by 0.5 mmol\/L lupanine, whereas the alkaloid did not stimulate insulin release with lower glucose concentrations. In islets treated with l-arginine, the potentiating effect of lupanine already occurred at 8 mmol\/L glucose. Lupanine increased the expression of the Ins-1 gene. The potentiating effect on secretion was correlated to membrane depolarization and an increase in the frequency of Ca2+ action potentials. Determination of the current through ATP-dependent K+ channels (KATP channels) revealed that lupanine directly inhibited the channel. The effect was dose-dependent but, even with a high lupanine concentration of  1 mmol\/L or after a prolonged exposure time (12 h), the KATP channel block was incomplete. Oral administration of lupanine did not induce hypoglycemia. By contrast, lupanine improved glycemic control in response to an oral glucose tolerance test in streptozotocin-diabetic rats. In summary, lupanine acts as a positive modulator of insulin release obviously without a risk for hypoglycemic episodes.<\/jats:p>","DOI":"10.3390\/molecules201019085","type":"journal-article","created":{"date-parts":[[2015,10,20]],"date-time":"2015-10-20T16:21:51Z","timestamp":1445358111000},"page":"19085-19100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Lupanine Improves Glucose Homeostasis by Influencing KATP Channels and Insulin Gene Expression"],"prefix":"10.3390","volume":"20","author":[{"given":"Mats","family":"Wiedemann","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, M\u00fcnster University, Corrensstra\u00dfe 48,  48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Gurrola-D\u00edaz","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Vargas-Guerrero","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44340 Guadalajara, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7875-4510","authenticated-orcid":false,"given":"Michael","family":"Wink","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg 69120, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Garc\u00eda-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Departamento de Bot\u00e1nica y Zoolog\u00eda, Centro Universitario de Ciencias Biol\u00f3gicas y Agropecuarias, Universidad de Guadalajara, 45110 Guadalajara, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"D\u00fcfer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Medicinal Chemistry, M\u00fcnster University, Corrensstra\u00dfe 48,  48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0300-483X(01)00555-8","article-title":"Biochemical study on the effects of some egyptian herbs in alloxan-induced diabetic rats","volume":"170","author":"Mansour","year":"2002","journal-title":"Toxicology"},{"key":"ref_2","first-page":"1261","article-title":"Hypoglycemic effect of cooked lupinus mutabilis and its purified alkaloids in subjects with type-2 diabetes","volume":"27","author":"Castro","year":"2012","journal-title":"Nutr. 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