The soybean peptide aglycin regulates glucose homeostasis in type 2 diabetic mice via IR/IRS1 pathway

Abstract

It has been previously reported that aglycin, a natural bioactive peptide isolated from soybean, is stable in digestive enzymes and has an antidiabetic potential. With a view to explore the pharmacological activity of aglycin in vivo, studies have been conducted to examine its therapeutic effect in diabetic mice, in which it was administered intragastrically as an oral agent. Diabetes was induced in BALB/c mice fed with a high-fat diet and a single intraperitoneal injection of streptozotocin. With onset of diabetes, the mice were administered daily with aglycin (50 mg/kg/d) for 4 weeks. Blood glucose was monitored once a week. Subsequently, skeletal muscle was isolated for assessment in terms of levels of gene and protein IR, IRS1, Akt and glucose transporter 4 (GLUT4). In addition, C2C12 muscle cells as an in vitro diabetic model were used to investigate the effect of aglycin on glucose uptake. Treatment with aglycin was found to be significantly effective in controlling hyperglycemia and improving oral glucose tolerance. Furthermore, aglycin enhanced glucose uptake and glucose transporter recruitment to the C2C12 cell surface in 10 min in vitro. Consistent with these effects, aglycin restored insulin signaling transduction by maintaining IR and IRS1 expression at both the mRNA and protein levels, as well as elevating the expression of p-IR, p-IRS1, p-Akt and membrane GLUT4 protein. The results hence demonstrate that oral administration of aglycin can potentially attenuate or prevent hyperglycemia by increasing insulin receptor signaling pathway in the skeletal muscle of streptozotocin/high-fat-diet-induced diabetic mice.