Methylglyoxal contributes to the development of insulin resistance and salt sensitivity in Sprague-Dawley rats.
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.
Guo
Qi
Q
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.
Mori
Takefumi
T
Jiang
Yue
Y
Hu
Chunyan
C
Osaki
Yusuke
Y
Yoneki
Yoshimi
Y
Sun
Ying
Y
Hosoya
Takuma
T
Kawamata
Akihiro
A
Ogawa
Susumu
S
Nakayama
Masaaki
M
Miyata
Toshio
T
Ito
Sadayoshi
S
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
D017127:Glycation End Products, Advanced; D017673:Sodium Chloride, Dietary; D017392:Thiobarbituric Acid Reactive Substances; D011765:Pyruvaldehyde; D012964:Sodium