Context: Gamma conglutin (Cc) 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 Cc from Lupinus rotundiflorus M. E. Jones (Fabaceae) modulates c-Jun Nterminal 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 ¼ 5): vehicle administration (HG-Ctrl), oral treatment with Cc (120 mg/kg/day) (HG-Lr) for one week, and treatment with metformin (300 mg/kg/day) (HG-Met); a healthy group (Ctrl, n ¼ 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 Cc 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 Cc decreased JNK1 phosphorylation. However, Cc did not change the levels of kidney and liver biomarkers. Discussion and conclusions: Treatment with Cc 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 Cc. Nevertheless, further studies are required.

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