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

Pharm Biol. 2021 Dec;59(1):374-380. doi: 10.1080/13880209.2021.1893757.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hypoglycemic Agents / isolation & purification
  • Hypoglycemic Agents / pharmacology
  • Lupinus / chemistry*
  • Male
  • Metformin / pharmacology
  • Mitogen-Activated Protein Kinase 8 / genetics
  • Plant Proteins / isolation & purification
  • Plant Proteins / pharmacology*
  • Rats
  • Rats, Wistar
  • Streptozocin

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Plant Proteins
  • Streptozocin
  • Metformin
  • Mitogen-Activated Protein Kinase 8

Grants and 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.