title: Hyperglycemia Enhances the Production of Amyloid β1-42 in the Lenses of Otsuka Long-Evans Tokushima Fatty Rats, a Model of Human Type 2 Diabetes.
abstract: OBJECTIVE
  It has been reported that the accumulation of amyloid β1-42 (Aβ1-42) in human lenses can cause some forms of lens opacification. However, the factors leading to changes in the accumulation of Aβ in the lens remain obscure. In this study, we investigate the effect of hyperglycemia on Aβ1-42 accumulation in lenses.
  
  
  METHODS
  Otsuka Long-Evans Tokushima Fatty (OLETF) rats and the human lens epithelial cell line SRA 01/04 (HLE cells) were used. The expression of mRNA was determined using a quantitative real-time RT-PCR method; Aβ1-42 levels were analyzed by an ELISA method.
  
  
  RESULTS
  Otsuka Long-Evans Tokushima Fatty rats at more than 20 weeks of age develop diabetes mellitus with hyperglycemia. Additionally, the levels of the mRNAs for Aβ1-42, amyloid precursor proteins (APP), β-(BACE1), and·γ-secretase (PS) rise in the lenses of OLETF rats with age; high Aβ1-42 levels are observed in the lens capsule-epithelium and cortex. The enhanced expression of the genes for APP, BACE1, and PS in the lenses of OLETF rats is prevented by food restriction (25 g/d/rat). When the effect of glucose levels on the production of Aβ1-42 was investigated in the human lens epithelial cell line SRA 01/04 (HLE cells), the mRNA levels for APP, BACE1, and PS, as well as Aβ1-42 protein levels, were significantly higher under high glucose conditions (20 mM) than under normal glucose conditions (5.6 mM).
  
  
  CONCLUSIONS
  High glucose leads to the increased expression of genes related to Aβ production, resulting in the accumulation of Aβ in the lens.
authors.affiliation: Faculty of Pharmacy Kinki University, Higashi-Osaka, Osaka, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Nagai
authors.affiliation: Faculty of Pharmacy Kinki University, Higashi-Osaka, Osaka, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Ophthalmology, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics* / Q000378:metabolism; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D051381:Rats; D020334:Rats, Inbred OLETF; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D001786:Blood Glucose; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D012313:RNA