Methylglyoxal contributes to the development of insulin resistance and salt sensitivity in Sprague-Dawley rats

Qi Guo, Takefumi Mori, Yue Jiang, Chunyan Hu, Yusuke Osaki, Yoshimi Yoneki, Ying Sun, Takuma Hosoya, Akihiro Kawamata, Susumu Ogawa, Masaaki Nakayama, Toshio Miyata, Sadayoshi Ito

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

Abstract

OBJECTIVES: 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. CONCLUSION: 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.

Original languageEnglish
Pages (from-to)1664-1671
Number of pages8
JournalJournal of hypertension
Volume27
Issue number8
DOIs
Publication statusPublished - 2009 Aug

Keywords

  • Advanced glycation endproducts
  • Diabetes
  • Hypertension
  • Insulin resistance
  • Methylglyoxal
  • Oxidative stress
  • Salt sensitivity

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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