title: Effects of phycocyanin on INS-1 pancreatic β-cell mediated by PI3K/Akt/FoxO1 signaling pathway.
abstract: The level of methylglyoxal (MG), which is a side-product of metabolic pathways, particularly in glycolysis, is elevated in diabetes. Notably, the accumulation of MG causes a series of pathological changes. Phycocyanin (PC) has been demonstrated to show insulin-sensitizing effect, however, the underlying molecular mechanism remains elusive. The aim of this study was to investigate the protective effects of PC on INS-1 rat insulinoma β-cell against MG-induced cell dysfunction, as well as the underlying mechanisms. PC was preliminarily verified to time-dependently activate PI3-kinase (PI3K) pathway, but the PI3K-specific inhibitor Wortmannin blocked the effect of PC. Glucose-stimulated insulin secretion (GSIS) was impaired in MG-treated INS-1 cells. Furthermore, MG induced dephosphorylation of Akt and FoxO1, resulting in nuclear localization and transactivation of FoxO1. Nevertheless, these effects were all effectively attenuated by PC. The ameliorated insulin secretion was related to the changes of FoxO1 mediated by PC, which demonstrated by RNA interference. And, the dosage used in the above experiments did not affect β-cell viability and apoptosis, although long-term MG induced cell apoptosis and mitochondrial dysfunction. In conclusion, PC was capable to protect INS-1 pancreatic β-cell against MG-induced cell dysfunction through modulating PI3K/Akt pathway and the downstream FoxO1.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yingnv
authors.initials: Y
authors.lastname: Gao
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Gaoyong
authors.initials: G
authors.lastname: Liao
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Chenxi
authors.initials: C
authors.lastname: Xiang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xuegan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Integrative Biology & Pharmacology, The University of Texas Health Science Center, Houston, USA. Electronic address: xiaodong.cheng@uth.tmc.edu.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: ouyu2008@126.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010798:Phycocyanin / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D000071161:Forkhead Box Protein O1
chemical_list: D051858:Forkhead Transcription Factors; D007004:Hypoglycemic Agents; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D010798:Phycocyanin; D051057:Proto-Oncogene Proteins c-akt; D011765:Pyruvaldehyde; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1
keywords: Akt; FoxO1; Methylglyoxal; Phycocyanin; β-Cell dysfunction