{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T19:42:56Z","timestamp":1773171776268,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Lupinus mutabilis (LM) is a legume part of Bolivian traditional diet that has a nutraceutical property reducing blood glucose levels. The prevalence of type 2 diabetes is increasing worldwide thus; the search for novel anti-diabetic drugs is needed. Based on its traditional use, we evaluated the anti-diabetic effect of LM in the spontaneously diabetic Goto-Kakizaki (GK) rat, a model of type 2 diabetes and in Wistar (W) rats as healthy control. LM seeds hydroethanolic extract, analyzed by gas chromatography-mass spectrometry and high-performance liquid chromatography-high resolution mass spectrometry, is a complex mixture of volatile and non-volatile components. A single oral administration of LM extract (2000 mg\/kg b.w.) improved glucose tolerance during the oral glucose tolerance test (OGTT) (30\u2013120 min) in GK and W rats (p &lt; 0.0001). The long-term treatment with LM (1000 mg\/kg b.w.), for 21 days, improved the area under the curve (AUC) of glucose during OGTT at day 20, in both GK (p &lt; 0.01) and W rats (p &lt; 0.01). The HbA1c (GK rats, p &lt; 0.05 and W rats, p &lt; 0.0001) and the non-fasting glucose (GK rats, p &lt; 0.05) were also reduced. LM increased both serum insulin levels (2.4-fold in GK rats and 2.5-fold W rats), and the glucose-induced (16.7 mM glucose) insulin release in isolated islets from treated animals (6.7-fold in GK rats, and 6.6-fold in W rats). Moreover, LM (10 mg\/mL) stimulated in vitro glucose induced (16.7 mM glucose) insulin release in batch incubated GK and W rat islets (p &lt; 0.0001). In perifused GK rat islets, insulin release in 16.7 mM glucose was increased 95.3-fold compared to untreated islets (p &lt; 0.0001), while no significant differences were found in perifused W rat islets. The LM mechanism of action, evaluated using inhibitory compounds of the insulin secretion pathway, showed that LM-dependent insulin secretion was reduced 42% by diazoxide (p &lt; 0.001), 70% by nifedipine (p &lt; 0.001), 86.7% by H89 (p &lt; 0.0001), 70.8% by calphostine-C (p &lt; 0.0001) and 93% by pertussis toxin (p &lt; 0.0001). A similar effect was observed in W rats islets. Our findings provide evidence that LM has an anti-diabetic effect through stimulation of insulin release. The effect is-dependent on L-type calcium channel, protein kinase A and C systems, and G protein-coupled exocytosis and is partially mediated by K-ATP channels.<\/jats:p>","DOI":"10.3390\/nu10070933","type":"journal-article","created":{"date-parts":[[2018,7,23]],"date-time":"2018-07-23T03:24:27Z","timestamp":1532316267000},"page":"933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Lupinus mutabilis Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats"],"prefix":"10.3390","volume":"10","author":[{"given":"Silvia","family":"Zambrana","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones Farmaco Bioquimicas, Universidad Mayor de San Andres, Avenida Saavedra, La Paz 2224, Bolivia"},{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna (L1:00), SE-171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena C. E.","family":"Lundqvist","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences, Swedish University of Agricultural Sciences, P.O. Box 7015, SE-750 07 Uppsala, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4163-8102","authenticated-orcid":false,"given":"Orlando","family":"Mamani","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Farmaco Bioquimicas, Universidad Mayor de San Andres, Avenida Saavedra, La Paz 2224, Bolivia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergiu-Bogdan","family":"Catrina","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna (L1:00), SE-171 76 Stockholm, Sweden"},{"name":"Department of Endocrinology and Metabolism, Karolinska University Hospital, 141 86 Stockholm, Sweden"},{"name":"Centrum for Diabetes, Academic Specialist Centrum, 14186 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Farmaco Bioquimicas, Universidad Mayor de San Andres, Avenida Saavedra, La Paz 2224, Bolivia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claes-G\u00f6ran","family":"\u00d6stenson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna (L1:00), SE-171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.diabres.2017.03.024","article-title":"IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040","volume":"128","author":"Ogurtsova","year":"2017","journal-title":"Diabetes Res. 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