title: 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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zeng
authors.forename: Wenrui
authors.initials: W
authors.lastname: Hou
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhang
authors.forename: Lulu
authors.initials: L
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Xi
authors.forename: Zhengwang
authors.initials: Z
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Xiang
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000188:drug therapy; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010940:Plant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D030262:Soybean Proteins / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004268:DNA-Binding Proteins; C528734:GLUT4 enhancer factor, mouse; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010940:Plant Proteins; D030262:Soybean Proteins; D014157:Transcription Factors; C580705:aglycin peptide, soybean; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose