title: Glucagon-like peptide 1 receptor plays an essential role in geniposide attenuating lipotoxicity-induced β-cell apoptosis.
abstract: β-Cell apoptosis is considered to be a major cause of loss of β cells in diabetes. Geniposide could prevent oxidative stress-induced neuron apoptosis, and improved glucose stimulated insulin secretion by activating glucagon-like peptide 1 receptor (GLP-1R) in INS-1 cells. Here we have investigated whether geniposide can exert a direct effect against pancreatic β-cell lipoapoptosis. The results indicated that pretreatment pancreatic INS-1 cells with geniposide for 7h attenuated palmitate-induced β-cell apoptosis and active caspase-3 expression, but this effect was disappeared at 18 h. Long-term incubation with palmitate decreased GLP-1R expression in INS-1 cells, and exendin (9-39), an antagonist for GLP-1R, inhibited the effect of geniposide on palmitate-induced apoptosis in INS-1 cells. Moreover, geniposide also improved the impairment of GLP-1R signaling through enhancing the phosphorylation of Akt and Foxo1, and increased the expression of PDX-1 in palmitate-treated INS-1 cells. These results suggest that geniposide inhibits early stage of lipotoxicity-induced β-cell apoptosis, and GLP-1R plays a critical role in geniposide counteracting the action of lipotoxicity in INS-1 pancreatic β cells.
authors: Research Centre of Medicinal Chemistry and Chemical Biology, Chongqing Technology and Business University, Chongqing 400067, China. jhliu@ctbu.edu.cn
authors: Jianhui
authors: J
authors: Liu
authors: Fei
authors: F
authors: Yin
authors: He
authors: H
authors: Xiao
authors: Lixia
authors: L
authors: Guo
authors: Xue
authors: X
authors: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004336:Drug Antagonism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D039823:Iridoids / Q000494:pharmacology*; D019308:Palmitic Acid / Q000633:toxicity*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D039823:Iridoids; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C007835:geniposide; D019308:Palmitic Acid; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D053148:Caspase 3