Effect of Lupinus rotundiflorus gamma conglutin treatment on JNK1 gene expression and protein activation in a rat model of type 2 diabetes

Abstract

Context

Gamma conglutin (Cγ) from lupine species represents a potential complementary treatment for type 2 diabetes mellitus (T2DM) because of its hypoglycaemic effect. However, its underlying mechanism of action is not fully known.

Objective

To evaluate whether Cγ from Lupinus rotundiflorus M. E. Jones (Fabaceae) modulates c-Jun N-terminal kinase 1 (JNK1) expression and activation in a T2DM rat model.

Materials and methods

Gamma conglutin isolated from L. rotundiflorus seeds was characterized by SDS-PAGE. Fifteen Wistar rats with streptozotocin-induced T2DM (HG) were randomized into three groups (n = 5): vehicle administration (HG-Ctrl), oral treatment with Cγ (120 mg/kg/day) (HG-Lr) for one week, and treatment with metformin (300 mg/kg/day) (HG-Met); a healthy group (Ctrl, n = 5) was included as control. The levels of glucose and biomarkers of renal and hepatic function were measured pre- and post-treatment. Hepatic Jnk1 expression and phosphorylation of JNK1 were evaluated by qRT-PCR and western blot, respectively.

Results

Oral treatment with either Cγ or metformin reduced serum glucose level to 86.30 and 74.80 mg/dL, respectively (p ˂ 0.05), from the basal levels. Jnk1 expression was 0.65- and 0.54-fold lower (p ˂ 0.05) in the HG-Lr and HG-Met groups, respectively, than in HG-Ctrl. Treatment with Cγ decreased JNK1 phosphorylation. However, Cγ did not change the levels of kidney and liver biomarkers.

Discussion and conclusions

Treatment with Cγ from L. rotundiflorus inhibited Jnk1 expression, in vivo, suggesting JNK1 as a potential therapeutic target in diabetes and revealing one mechanism underlying the hypoglycaemic effect of lupine Cγ. Nevertheless, further studies are required.

Keywords:

• Hypoglycaemic effect
• insulin resistance
• legume
• lupine
• vegetal protein

Acknowledgments

The authors thank Adrián Ramírez de Arellano and Lucía De la Cruz Color for their valuable technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Apoyo a la Incorporación de NPTC SEP-PRODEP under Grant UDG-PTC-1293; and partially supported by the University of Guadalajara under Grants REC/164/2017, REC/CINV/325/2018, and REC/0964/19.