Identification of the bioactive and consensus peptide motif from Momordica charantia insulin receptor-binding protein

• Published in: Food chemistry 2016-08, Vol.204, p.298-305
• Main Authors: Lo, Hsin-Yi, Li, Chia-Cheng, Ho, Tin-Yun, Hsiang, Chien-Yun
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Bioactive peptide motif; Blood Glucose - metabolism; Cell Line; Conserved Sequence; Diabetes Mellitus, Experimental - metabolism; Humans; Hypoglycemic; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - metabolism; Insulin - metabolism; Insulin receptor-binding protein; Male; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Momordica charantia - chemistry; Phosphorylation; Plant Proteins - chemistry; Plant Proteins - metabolism; Protein Binding; Receptor, Insulin - chemistry; Receptor, Insulin - metabolism; Signal Transduction; β hairpin
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2016.02.135

•An IR-binding peptide motif was identified from bitter melon proteins.•Bioactive peptide stimulated IR kinase activity and activated IR signaling pathway.•Bioactive peptide stimulated glucose uptake in cells and glucose clearance in mice.•Bioactive peptides were present in plants and shared a similar β-hairpin motif. Many food bioactive peptides with diverse functions have been discovered by studying plant proteins. We have previously identified a 68-residue insulin receptor (IR)-binding protein (mcIRBP) from Momordica charantia that exhibits hypoglycemic effects in mice via interaction with IR. By in vitro digestion, we found that mcIRBP-19, spanning residues 50–68 of mcIRBP, enhanced the binding of insulin to IR, stimulated the phosphorylation of PDK1 and Akt, induced the expression of glucose transporter 4, and stimulated both the uptake of glucose in cells and the clearance of glucose in diabetic mice. Furthermore, mcIRBP-19 homologs were present in various plants and shared similar β-hairpin structures and IR kinase-activating abilities to mcIRBP-19. In conclusion, our findings suggested that mcIRBP-19 is a blood glucose-lowering bioactive peptide that exhibits IR-binding potentials. Moreover, we newly identified novel IR-binding bioactive peptides in various plants which belonged to different taxonomic families.