title: Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation.
abstract: Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Zai
authors.identifier: 0000-0002-8548-1362
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Xu
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Deng
authors.affiliation: Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: Jinning
authors.identifier: 0000-0002-7793-5029
authors.initials: J
authors.lastname: Lou
mesh_terms: D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017127:Glycation End Products, Advanced; D007328:Insulin; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose