title: Methylglyoxal contributes to the development of insulin resistance and salt sensitivity in Sprague-Dawley rats.
abstract: OBJECTIVE
  Methylglyoxal, a metabolite of the glycolysis pathway, may play an important role in the development of diabetes and hypertension, but the exact mechanism has not been fully elucidated. The present study was designed to investigate whether methylglyoxal could directly induce insulin resistance and salt sensitivity in Sprague-Dawley rats.
  
  
  METHODS
  Rats were allocated to four groups: control (normal drinking water), 1% methylglyoxal in drinking water, 1% methylglyoxal plus N-acetyl cysteine (NAC) (800 mg/kg per day), a methylglyoxal scavenger, or TM2002 (100 mg/kg per day), an advanced glycation endproducts (AGEs) inhibitor. After 4-week treatment insulin resistance was evaluated by an euglycemic hyperinsulinemic glucose clamp technique. In another set of rats, either a high-salt diet (4%) alone, standard rat chow with 1% methylglyoxal in drinking water or high-salt diet plus methylglyoxal was given for 4 weeks. Immunohistochemistry was performed to measure nitrotyrosine and methylglyoxal-induced AGEs, N-carboxyethyl-lysine (CEL) in the kidney.
  
  
  RESULTS
  Four-week treatment with NAC or TM2002 completely improved methylglyoxal-induced insulin resistance. Co-administration of methylglyoxal and high-salt diet significantly increased systolic blood pressure, urinary albumin excretion, urinary thiobarbituric acid-reactive substances excretion and the renal nitrotyrosine expression in the kidney (markers of oxidative stress) compared with methylglyoxal or high-salt diet alone. Renal CEL was significantly increased in methylglyoxal-treated rats compared with nonmethylglyoxal-treated rats.
  
  
  CONCLUSIONS
  These results indicate that methylglyoxal-induced insulin resistance and salt sensitivity at least in part by increasing oxidative stress and/or AGEs formation in Sprague-Dawley rats. The present study provides further evidence for methylglyoxal as one of the causative factors in the pathogenesis of insulin resistance and salt-sensitive hypertension.
authors.affiliation: Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
authors.forename: Qi
authors.initials: Q
authors.lastname: Guo
authors.forename: Takefumi
authors.initials: T
authors.lastname: Mori
authors.forename: Yue
authors.initials: Y
authors.lastname: Jiang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Osaki
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Yoneki
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Takuma
authors.initials: T
authors.lastname: Hosoya
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kawamata
authors.forename: Susumu
authors.initials: S
authors.lastname: Ogawa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakayama
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyata
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001823:Body Composition; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006973:Hypertension / Q000209:etiology*; D007150:Immunohistochemistry; D007333:Insulin Resistance; D007668:Kidney / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D011765:Pyruvaldehyde / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D017127:Glycation End Products, Advanced; D017673:Sodium Chloride, Dietary; D017392:Thiobarbituric Acid Reactive Substances; D011765:Pyruvaldehyde; D012964:Sodium