title: Geniposide protects pancreatic β cells from high glucose-mediated injury by activation of AMP-activated protein kinase.
abstract: Our previous works indicated that geniposide could regulate glucose-stimulated insulin secretion (GSIS), and improved chronic high glucose-induced dysfunctions in pancreatic β cells, but the molecular mechanisms remain largely unknown. In the present study, we investigated the role of 5'-AMP-activated protein kinase (AMPK) in high glucose induced cell injury and explored the associated molecular mechanisms in rat INS-1 pancreatic β cells. Data suggested that geniposide obviously prevented the cell damage induced by high (25 mM) glucose in INS-1 cells, which increased the protein levels of cell apoptosis-associated enzymes, including heme oxygenase-1 (HO-1), and Bcl-2, but apparently attenuated the protein level of Bax, an apoptotic protein. In addition, Compound C, an AMPK inhibitor, remarkably inhibited the effects of geniposide on the protein levels of HO-1, Bcl-2, and Bax, but AICAR, an AMPK activator, potentiated the role of geniposide on the protein levels of HO-1, Bcl-2, and Bax. More importantly, geniposide directly prevented the cleavage of caspase-3 induced by high glucose, and this effect was also evidently prohibited by the pre-incubation of compound C in high glucose-treated INS-1 cells. Furthermore, using the method of RNA interfere, we further proved that treatment with AMPK siRNA attenuated the effects of geniposide on the apoptosis-associated proteins and cell viability. All these data suggest that AMPK plays a crucial role on geniposide antagonizing high glucose-induced pancreatic β cells injury.
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry and Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry and Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry and Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry and Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China.
authors.forename: Yonglan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry and Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D039823:Iridoids / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D039823:Iridoids; D020011:Protective Agents; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; C007835:geniposide; D051547:Heme Oxygenase-1; D055372:AMP-Activated Protein Kinases; D053148:Caspase 3; D005947:Glucose
keywords: 5′-AMP-activated protein kinase (AMPK); Bax; Bcl-2; Caspase-3; geniposide; glucose-stimulated insulin secretion (GSIS)