title: Caffeic acid, naringenin and quercetin enhance glucose-stimulated insulin secretion and glucose sensitivity in INS-1E cells.
abstract: OBJECTIVE
  Caffeic acid, naringenin and quercetin are naturally occurring phenolic compounds (PCs) present in many plants as secondary metabolites. The aim of this study was to investigate their effect on glucose-stimulated insulin secretion (GSIS) in INS-1E cells and to explore their effect on expression of genes involved in β-cell survival and function under normoglycaemic and glucotoxic conditions.
  
  
  METHODS
  For acute studies, INS-1E cells were grown in 11 mM glucose (72 h) and then incubated with the PCs (1 h) with 3.3/16.7 mM glucose; whereas, for chronic studies, the cells were grown in 11 mM glucose (72 h) with/without the PCs, and then incubated with 3.3/16.7 mM glucose (1 h); thereafter, GSIS was measured. For GSIS and gene expression studies (GES) under glucotoxic conditions, two sets of cells were grown in 11/25 mM glucose with/without the PCs (72 h): one was used for GES, using real time RT-PCR, and the other was exposed to 3.3/16.7 mM glucose, followed by measurement of GSIS.
  
  
  RESULTS
  The study demonstrated that the PCs can enhance GSIS under hyperglycaemic and glucotoxic conditions in INS-1E cells. Moreover, these compounds can differentially, yet distinctly change the expression profile of genes [Glut2 (glucose transporter 2), Gck (glucokinase), Ins1 (insulin 1), Ins2, Beta2 (neurogenic differentiation protein 1), Pdx1 (pancreatic and duodenal homeobox protein 1), Akt1 (RAC-α serine/threonine-protein kinase encoding gene), Akt2 (RAC-β serine/threonine-protein kinase encoding gene), Irs1 (insulin receptor substrate 1), Acc1 (acetyl CoA carboxylase 1), Bcl2 (β-cell lymphoma 2 protein), Bax (Bcl-2 associated X protein), Casp3 (Caspase 3), Hsp70 (heat shock protein 70), and Hsp90] involved in β-cell stress, survival and function.
  
  
  CONCLUSIONS
  The results indicate that the PCs tested enhance GSIS and glucose sensitivity in INS-1E cells. They also modulate gene expression profiles to improve β-cell survival and function during glucotoxicity.
authors.affiliation: Department of Food Science, Aarhus University, Tjele, Denmark.
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: N
authors.initials: N
authors.lastname: Oksbjerg
authors.forename: J F
authors.initials: JF
authors.lastname: Young
authors.forename: P B
authors.initials: PB
authors.lastname: Jeppesen
mesh_terms: D000818:Animals; D001692:Biological Transport; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D044950:Flavanones / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D055571:Secretory Pathway / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D002109:Caffeic Acids; D044950:Flavanones; D007328:Insulin; D028321:Plant Preparations; D012333:RNA, Messenger; D011794:Quercetin; D005941:Glucokinase; C005273:naringenin; D005947:Glucose; C040048:caffeic acid
keywords: INS-1E cells; gene expression; glucotoxicity; hyperglycaemia; insulin secretion; phenolic compounds; type 2 diabetes; β cells