title: Geniposide improves insulin production and reduces apoptosis in high glucose-induced glucotoxic insulinoma cells.
abstract: Our previous work revealed that in the pancreatic β cell line, geniposide modulated ATP production and glucose-stimulated insulin secretion (GSIS) induced by the acute stimulation of high glucose concentration. However, the effects of geniposide on functional impairment and the mass of β-cells exposed to elevated levels of glucose remains unknown. In the present study, impaired GSIS and restrained proliferation were observed in the prolonged culture of insulinoma INS-1 cells with 33mM of glucose (high glucose). Our results indicate that the glucose-induced impairment of insulin release was significantly reverted by the inclusion of 1 or 10μM of geniposide. Moreover, induction of the phosphorylation of AMP-activated protein kinase (AMPK) was observed, which promoted the utilization of nutrient stores for energy production. AMPK phosphorylation was enhanced by an increased number of INS-1 cells, and the increased expression of AMPK downstream target heme oxygenase 1 (HO-1), under high glucose concentration. Furthermore, geniposide protected rat insulinoma cells from apoptosis in high-glucose concentrations. We have shown that these effects were associated with an increased apoptosis-related Bcl-2/BAX protein ratio. In conclusion, geniposide dose dependently improves β-cell function and increases the proliferation of β-cells exposed to prolonged hyperglycemia.
authors.affiliation: Chongqing Key Lab of Natural Medicine Research, Chongqing Technology and Business University, Chongqing 400067, China. Electronic address: 80074241@qq.com.
authors.forename: L X
authors.initials: LX
authors.lastname: Guo
authors.affiliation: Chongqing Key Lab of Natural Medicine Research, Chongqing Technology and Business University, Chongqing 400067, China; College of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400050, China.
authors.forename: J H
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Chongqing Key Lab of Natural Medicine Research, Chongqing Technology and Business University, Chongqing 400067, China.
authors.forename: X X
authors.initials: XX
authors.lastname: Zheng
authors.affiliation: Chongqing Key Lab of Natural Medicine Research, Chongqing Technology and Business University, Chongqing 400067, China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Yin
authors.affiliation: Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
authors.forename: J
authors.initials: J
authors.lastname: Kosaraju
authors.affiliation: Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
authors.forename: K Y
authors.initials: KY
authors.lastname: Tam
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection; D005947:Glucose / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007328:Insulin / Q000096:biosynthesis*; D007340:Insulinoma; D039823:Iridoids / Q000494:pharmacology*; D051381:Rats
chemical_list: D007328:Insulin; D039823:Iridoids; C007835:geniposide; D005947:Glucose
keywords: Apoptosis; Geniposide; Glucose-stimulated insulin secretion; Glucotoxicity