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Lupinus mutabilis Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats.
Nutrients 2018; 10(7)N

Abstract

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) (30⁻120 min) in GK and W rats (p < 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 < 0.01) and W rats (p < 0.01). The HbA1c (GK rats, p < 0.05 and W rats, p < 0.0001) and the non-fasting glucose (GK rats, p < 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 < 0.0001). In perifused GK rat islets, insulin release in 16.7 mM glucose was increased 95.3-fold compared to untreated islets (p < 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 < 0.001), 70% by nifedipine (p < 0.001), 86.7% by H89 (p < 0.0001), 70.8% by calphostine-C (p < 0.0001) and 93% by pertussis toxin (p < 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.

Authors+Show Affiliations

Instituto de Investigaciones Farmaco Bioquimicas, Universidad Mayor de San Andres, Avenida Saavedra, La Paz 2224, Bolivia. sil_zambrana@yahoo.es. Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna (L1:00), SE-171 76 Stockholm, Sweden. sil_zambrana@yahoo.es.Department of Molecular Sciences, Swedish University of Agricultural Sciences, P.O. Box 7015, SE-750 07 Uppsala, Sweden. lena.lundqvist@slu.se.Instituto de Investigaciones Farmaco Bioquimicas, Universidad Mayor de San Andres, Avenida Saavedra, La Paz 2224, Bolivia. you_dinhi@hotmail.com.Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna (L1:00), SE-171 76 Stockholm, Sweden. Sergiu-Bogdan.Catrina@ki.se. Department of Endocrinology and Metabolism, Karolinska University Hospital, 141 86 Stockholm, Sweden. Sergiu-Bogdan.Catrina@ki.se. Centrum for Diabetes, Academic Specialist Centrum, 14186 Stockholm, Sweden. Sergiu-Bogdan.Catrina@ki.se.Instituto de Investigaciones Farmaco Bioquimicas, Universidad Mayor de San Andres, Avenida Saavedra, La Paz 2224, Bolivia. eduardo.gonzales@gmail.com.Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Solna (L1:00), SE-171 76 Stockholm, Sweden. Claes-Goran.Ostenson@ki.se.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30037028

Citation

Zambrana, Silvia, et al. "Lupinus Mutabilis Extract Exerts an Anti-Diabetic Effect By Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats." Nutrients, vol. 10, no. 7, 2018.
Zambrana S, Lundqvist LCE, Mamani O, et al. Lupinus mutabilis Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats. Nutrients. 2018;10(7).
Zambrana, S., Lundqvist, L. C. E., Mamani, O., Catrina, S. B., Gonzales, E., & Östenson, C. G. (2018). Lupinus mutabilis Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats. Nutrients, 10(7), doi:10.3390/nu10070933.
Zambrana S, et al. Lupinus Mutabilis Extract Exerts an Anti-Diabetic Effect By Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats. Nutrients. 2018 Jul 20;10(7) PubMed PMID: 30037028.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lupinus mutabilis Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats. AU - Zambrana,Silvia, AU - Lundqvist,Lena C E, AU - Mamani,Orlando, AU - Catrina,Sergiu-Bogdan, AU - Gonzales,Eduardo, AU - Östenson,Claes-Göran, Y1 - 2018/07/20/ PY - 2018/06/05/received PY - 2018/07/09/revised PY - 2018/07/16/accepted PY - 2018/7/25/entrez PY - 2018/7/25/pubmed PY - 2018/10/30/medline KW - Goto-Kakizaki rats KW - Lupinus mutabilis KW - diabetes mellitus type 2 diabetes KW - insulin secretion KW - natural product KW - nutraceutical JF - Nutrients JO - Nutrients VL - 10 IS - 7 N2 - 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) (30⁻120 min) in GK and W rats (p < 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 < 0.01) and W rats (p < 0.01). The HbA1c (GK rats, p < 0.05 and W rats, p < 0.0001) and the non-fasting glucose (GK rats, p < 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 < 0.0001). In perifused GK rat islets, insulin release in 16.7 mM glucose was increased 95.3-fold compared to untreated islets (p < 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 < 0.001), 70% by nifedipine (p < 0.001), 86.7% by H89 (p < 0.0001), 70.8% by calphostine-C (p < 0.0001) and 93% by pertussis toxin (p < 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. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/30037028/Lupinus_mutabilis_Extract_Exerts_an_Anti_Diabetic_Effect_by_Improving_Insulin_Release_in_Type_2_Diabetic_Goto_Kakizaki_Rats_ L2 - http://www.mdpi.com/resolver?pii=nu10070933 DB - PRIME DP - Unbound Medicine ER -