title: Regulation of insulin secretion by geniposide: possible involvement of phosphatidylinositol 3-phosphate kinase.
abstract: OBJECTIVE
  Type 2 diabetes mellitus is characterized by lack of, or relative deficiency in, insulin productions and insensitivity of target tissues to insulin. Improvement of β-cell functions is a potential strategy for the clinical management of this disease. We reported before that geniposide improved glucose-stimulated insulin secretion with the activation of glucagon-like peptide 1 receptor (GLP-1R) in INS-1 pancreatic β cells, but the cell signaling mechanism of geniposide regulating glucose-stimulated insulin secretion (GSIS) in β cells is so far poorly understood.
  
  
  METHODS
  Effect of LY294002, a specific inhibitor of PI3K, on GSIS in the presence or absence of geniposide in INS-1 cells. In addition, the differential protein expression of geniposide treated INS-1 cells was examined by Western blot.
  
  
  RESULTS
  After pretreatment with 10 µM LY294002 for 1 hour, the insulin secretion induced by geniposide was partly abolished in INS-1 cells. After treatment with geniposide, the phosphorylation of PDK1 and Akt473 increased gradually to the maximum at 60 minutes or 120 minutes respectively. Furthermore, geniposide also inhibited the phosphorylation of downstream target GSK3β, and this effect was counteracted by preincubation with LY294002. And the expression of GLUT2 was increased after treatment with different doses geniposide.
  
  
  CONCLUSIONS
  Geniposide increases insulin secretion in pancreatic β cells in a PI3K dependent mechanism potentially through increased GLUT2 protein levels.
authors.affiliation: Chongqing Key Lab of Catalysis & Functional Organic Molecules, Chongqing Key Lab of Natural Medicine Research, Key Laboratory of Catalysis Science and Technology of Chongqing Education Commission; Chongqing Technology and Business University, Chongqing, China. jhliu@ctbu.edu.cn.
authors.forename: L X
authors.initials: LX
authors.lastname: Guo
authors.forename: J H
authors.initials: JH
authors.lastname: Liu
authors.forename: F
authors.initials: F
authors.lastname: Yin
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000187:drug effects / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D039823:Iridoids / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D051273:Glucose Transporter Type 2; D007004:Hypoglycemic Agents; D007328:Insulin; D039823:Iridoids; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D018027:Receptors, Glucagon; C495683:Slc2a2 protein, rat; C007835:geniposide; D058539:Phosphatidylinositol 3-Kinase; D064413:3-Phosphoinositide-Dependent Protein Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; C578579:Pdpk1 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose