title: Advanced glycation end products downregulate glucokinase in mice.
abstract: BACKGROUND
  Glucokinase, the enzyme that catalyses the conversion of glucose to G-6-P, plays a key role in glucose metabolism. AGEs are implicated in diabetic complications. A previous study reported that AGEs decreased β-cell function through inhibition of cytochrome c oxidase and adenosine triphosphate synthesis. This study investigated the effects of AGEs on glucokinase and islet function.
  
  
  METHODS
  Six-month-old male C57BL6 mice were divided into bovine serum albumin (BSA) and AGE-BSA groups. BSA (200 µg/g) and AGE-BSA (60 U/g) were administered intraperitoneally twice daily. After 2 weeks, serum AGE levels were measured, oral glucose tolerance test was performed, and insulin levels during the oral glucose tolerance test were determined. Glucokinase protein expression level and activity were measured in pancreatic islets.
  
  
  RESULTS
  We observed that the normal mice (C57/BL6) treated for 2 weeks with AGE-BSA showed impaired glucose tolerance and decrease in acute insulin release. Glucokinase activity in islets from the AGE-BSA-treated mice was significantly inhibited and accompanied by blunted response of islets to high glucose stimulation. Moreover, in vitro experiments showed that glucokinase protein expression was decreased, its activity was inhibited, and islet function was decreased. GKA partially restored glucokinase activity and islet function caused by AGEs.
  
  
  CONCLUSIONS
  We concluded that AGEs inhibited glucokinase activity, leading to islet dysfunction in mouse pancreatic islets.
authors.affiliation: Department of Anesthesiolgy and Pain Medicine, Catholic Unversity of Saint Vincent Hospital, Suwon, Republic of Korea.
authors.forename: Hongsoo
authors.initials: H
authors.lastname: Jung
authors.forename: Jindeok
authors.initials: J
authors.lastname: Joo
authors.forename: Yeonsu
authors.initials: Y
authors.lastname: Jeon
authors.forename: Junga
authors.initials: J
authors.lastname: Lee
authors.forename: Janghyeok
authors.initials: J
authors.lastname: In
authors.forename: Daewoo
authors.initials: D
authors.lastname: Kim
authors.forename: Eujin
authors.initials: E
authors.lastname: Kang
authors.forename: Yongshin
authors.initials: Y
authors.lastname: Kim
authors.forename: Yonggul
authors.initials: Y
authors.lastname: Lim
authors.forename: Jaehyeok
authors.initials: J
authors.lastname: Kang
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Choi
mesh_terms: D000818:Animals; D015536:Down-Regulation; D005941:Glucokinase / Q000187:drug effects / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012710:Serum Albumin, Bovine; D013450:Sulfones / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: C503863:2-cyclohexyl-1-(4-methanesulfonylphenyl)cyclopropanecarboxylic acid thiazol-2-ylamide; D017127:Glycation End Products, Advanced; D007328:Insulin; D013450:Sulfones; D013844:Thiazoles; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D005941:Glucokinase