title: Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic β-cells.
abstract: BACKGROUND
  Glycated albumin (GA) is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic β cells.
  
  
  METHODS
  Islets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA) and GA was measured under three different glucose concentrations, 3 mM (G3), 7 mM (G7), and 15 mM (G15), with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS), and the expression of iNOS-mRNA was investigated by real-time PCR.
  
  
  RESULTS
  Insulin secretion in the presence of HA and GA was 20.9 ± 3.9 and 21.6 ± 5.5 μU/3 islets/h for G3 (P = 0.920), and 154 ± 9.3 and 126.1 ± 7.3 μU/3 islets/h (P = 0.046), for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion.
  
  
  CONCLUSIONS
  GA suppresses glucose-induced insulin secretion from rat pancreatic β-cells through impairment of intracellular glucose metabolism.
authors.affiliation: Second Department of Surgery, Dokkyo Medical University, School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan. tsawada@dokkyomed.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shiraki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Miura
authors.forename: Tokihiko
authors.initials: T
authors.lastname: Sawada
authors.forename: Toshie
authors.initials: T
authors.lastname: Okada
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Sakuraoka
authors.forename: Takashi
authors.initials: T
authors.lastname: Muto
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kubota