title: GLP-1 ameliorates the proliferation activity of INS-1 cells inhibited by intermittent high glucose concentrations through the regulation of cyclins.
abstract: Glucagon-like peptide-1 (GLP-1) and its analog exendin (EX)-4 have been considered to promote β-cell growth and expansion. In the present, study we investigated the effect of GLP-1 on proliferative activity and cell cycle regulation in the pancreatic insulin-secreting β-cell line, INS-1, treated with intermittent high glucose. INS-1 cells were treated with normal glucose (5.5 mmol/l), constant high glucose (30 mmol/l) and intermittent high glucose (rotation/24 h in 5.5 or 30 mmol/l) in the presence or absence of GLP-1 (100 nmol/l) for seven days. Proliferative activity, cell cycle and the expression of cyclin D1, p21, p27 and Skp2 were examined. INS-1 treated with intermittent high glucose and GLP-1 demonstrated a significant increase in proliferation activity (1.45±0.12; P<0.01) and decreased cell proportion in G0/G1 phase (49.73±4.04%, P<0.01) compared with those without GLP-1. Furthermore, the expression levels of cyclin D1 and Skp2 were increased, while the expression of p27 and p21 were significantly reduced. Similar results were identified in those treated with constant high glucose and GLP-1. These results suggest that GLP-1 may ease the G0/G1 cell cycle arrest of INS-1 cells induced by intermittent high glucose by upregulating the expression of cyclin D1 and Skp2, downregulating the expression of p21 and p27, and finally promoting the cell cycle progression and proliferation activity.
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Nanshan Affiliated Hospital of Guangdong Medical College, Shenzhen, Guangdong, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Function Department of Nanshan Maternal and Child's Hospital, Shenzhen, Guangdong, P.R. China.
authors.forename: Xinkui
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Dehong
authors.initials: D
authors.lastname: Cai
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D051381:Rats; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D044786:S-Phase Kinase-Associated Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D052216:Glucagon-Like Peptide 1; D005947:Glucose