title: Geniposide accelerates proteasome degradation of Txnip to inhibit insulin secretion in pancreatic β-cells.
abstract: OBJECTIVE
  To analyze the role of geniposide in the protein degradation of Txnip and to determine the impact of Txnip on geniposide-regulated GSIS in pancreatic INS-1 cells.
  
  
  METHODS
  The content of Txnip protein was measured by western blot; insulin content and glucose uptake were determined by ELISA; and knockdown of Txnip was the method of RNA interference.
  
  
  RESULTS
  Glucose induces a rapid increase in Txnip protein, and geniposide accelerates the degradation of Txnip via proteasome pathway in the presence of high glucose (25 mM) in INS-1 pancreatic β-cells. And MG132, a proteasomal inhibitor, potentiates glucose uptake, metabolism (ATP production) and glucose-stimulated insulin secretion (GSIS) in high-glucose (25 mM)-treated INS-1 cells, but geniposide significantly prevents these effects. Furthermore, the combination of geniposide and Txnip knockdown shows substantial synergistic effects to reduce glucose uptake, metabolism and GSIS in high-glucose (25 mM)-treated INS-1 cells.
  
  
  CONCLUSIONS
  Txnip protein played an essential role in glucose uptake, metabolism and GSIS, and geniposide could accelerate the degradation via proteasome pathway in high-glucose-treated pancreatic INS-1 cells.
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Liu
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China.
authors.forename: Y N
authors.initials: YN
authors.lastname: Hao
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China. fyin@cqut.edu.cn.
authors.forename: F
authors.initials: F
authors.lastname: Yin
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Zhang
authors.affiliation: Chongqing Key Lab of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, China. jhliu@cqut.edu.cn.
authors.forename: J H
authors.initials: JH
authors.lastname: Liu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007340:Insulinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D039823:Iridoids / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D007328:Insulin; D039823:Iridoids; C493796:TXNIP protein, rat; C007835:geniposide; D046988:Proteasome Endopeptidase Complex; D005947:Glucose
keywords: Geniposide; Glucose-stimulated insulin secretion (GSIS); Proteasome degradation; Thioredoxin-interacting protein (Txnip); Type 2 diabetes mellitus (T2DM)