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

Context Gamma conglutin (C gamma) 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 C gamma 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 C gamma (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 C gamma 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 C gamma decreased JNK1 phosphorylation. However, C gamma did not change the levels of kidney and liver biomarkers. Discussion and conclusions Treatment with C gamma 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 C gamma. Nevertheless, further studies are required.

Automated summary

The study demonstrated that C gamma from Lupinus rotundiflorus and metformin significantly reduced blood glucose levels in rats with type 2 diabetes mellitus, and also inhibited the expression of JNK1, suggesting a potential therapeutic target for diabetes treatment.