Planta Medica International Open 2017; 4(S 01): S1-S202
DOI: 10.1055/s-0037-1608404
Poster Session
Georg Thieme Verlag KG Stuttgart · New York

Lupinus mutabilis extract improves insulin secretion in Diabetic Goto-Kakizaki rats

S Zambrana
1   Instituto de Investigaciones Farmaco Bioquimicas, Universidad Mayor de San Andres, La Paz, Bolivia
2   Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
,
O Mamani
1   Instituto de Investigaciones Farmaco Bioquimicas, Universidad Mayor de San Andres, La Paz, Bolivia
,
SB Catrina
2   Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
,
E Gonzales
1   Instituto de Investigaciones Farmaco Bioquimicas, Universidad Mayor de San Andres, La Paz, Bolivia
,
CG Ostenson
2   Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2017 (online)

 

The prevalence of type 2 diabetes is increasing worldwide and therefore investigation to develop novel therapeutic strategies is needed. Based on the use of Bolivian traditional foods, the aim of this study is to evaluate the anti-diabetic nutraceutical property of Lupinus mutabilis (LM) [1]. The type 2 diabetic model, Goto-Kakizaki rats (GK), was used. In the Oral Glucose Tolerance test (OGTT) LM (2000 mg/kg b.w.), by single oral administration, improved glucose tolerance, expressed by the area under the glucose curve (AUC), 1005.0 ± 57.59mM/120 min vs. placebo 1379.7 ± 132.5 mM/120 min (p < 0.05). The LM long-term treatment (1000 mg/kg b.w.), for 21 days, improved the AUC under the OGTT (827.3 ± 24.80 mM/120 min) vs. value before treatment (1050 ± 26.96 mM/120 min) (p < 0.05). Moreover, LM long-term treatment increased serum insulin levels, after 30 min of glucose challenge, 2.4-fold at day 20 (58.2 ± 2.3µU/ml) vs. GK placebo (24.6 ± 0.8µU/ml) (p < 0.0001). Glycated hemoglobin, HbA1c, was reduced at day 20 by 30% vs. placebo group (p < 0.01). In vitro studies showed that LM (10 mg/ml) stimulates insulin secretion in GK batch incubated islets, at 16.7 mM glucose, 3.3-fold increase (118.9 ± 4.8µU/islets/h vs. 35.1 ± 3.7µU/islet/h, untreated islets) (p < 0.0001). The LM mechanism of action was evaluated using inhibitory compounds of insulin secretion pathway. Insulin secretion of LM (104.7 ± 6.9) was reduced 42% by Diazoxide (60.4 ± 3.2µU/islet/h) (p < 0.001), 70% by calcium-blocker Nifedipine (31.2 ± 3.1µU/islet/h) (p < 0.001), 86.7% by protein kinas A (PKA) blocker, H89 (13.8 ± 1.0µU/islet/h) (p < 0.0001), 70.8% by PKC-blocker Calphostine-C (30.6 ± 1.5µU/islet/h) (p < 0.0001) and 93% by Pertussis toxin, inhibiting insulin exocytosis (7.3 ± 0.9µU/islet/h) (p < 0.0001). Our findings provide evidence of LM anti-diabetic effect explained by stimulation of insulin release, dependent on L-type calcium channels, PKA and PKC system and insulin exocytosis.

[1] Fornasini, M, et al, Nutricion Hospitalaria, 2012. 27:425 – 433.