title: Agaricus bisporus lectins mediates islet β-cell proliferation through regulation of cell cycle proteins.
abstract: This study was designed to determine the therapeutic effect of Agaricus bisporus lectins (ABL) by the regeneration of β-cells in mice following 70% partial pancreatectomy (PPx), and to explore the mechanisms of ABL-induced β-cell proliferation. Adult C57BL/6J mice were subjected to a 70% PPx operation or a sham operation, and mice received 10 mg/kg body weight of ABL or saline immediately after surgery. Blood glucose concentrations and insulin secretion levels were measured. To determine the growth rates of β-cells and duct cells, immunohistological analysis of pancreatic tissues was performed. Key cell cycle proteins and β-cell specific genes were measured by realtime polymerase chain reaction, Western blotting and immunohistological staining. In this study, a significant decrease in blood glucose concentrations, increase in glucose tolerance and expanded β-cell mass were observed in the ABL-treated mice. At the same time, after ABL treatment, increased β-cell proliferation rates were observed. Further studies on the expression of cyclin D1, cyclin D2 and Cdk4 demonstrated that these genes were significantly up-regulated in the ABL-treated mice. Meanwhile, Cdk4 activity was also enhanced. Moreover, the expression of PDX-1 (pancreatic and duodenal homeobox 1), Ngn3 (neurogenin 3), insulin, GLUT-1 (glucose transporter 1) and glucokinase was also increased in the ABL-treated mice. These findings demonstrate that ABL administration could partially reverse the impaired β-cell growth potential by regulating cell cycle proteins. Induction of islet β-cell proliferation by ABL suggests the therapeutic potential in preventing and/or treating diabetes.
authors.affiliation: School of Life Science, Sichuan University, Chengdu, Sichuan 610064, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuande
authors.initials: Y
authors.lastname: Liu
authors.forename: Hailian
authors.initials: H
authors.lastname: Wang
authors.forename: Chunyang
authors.initials: C
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: Qi
authors.forename: Jinku
authors.initials: J
authors.lastname: Bao
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000378:metabolism*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D037102:Lectins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010180:Pancreatectomy; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C041433:Agaricus lectins; D001786:Blood Glucose; D018797:Cell Cycle Proteins; D007328:Insulin; D037102:Lectins