[Amelioration of insulin resistance after scald by c-Jun N-terminal kinase inhibitor in rat].
OBJECTIVE
To investigate the role and mechanism of c-Jun N-terminal kinase (JNk) inhibitor (SP600125) in amelioration of insulin resistance after scald.


METHODS
Twenty-four Sprague-Dawley rats were randomized into sham (the process of scald was mimicked by water at room temperature) , scald, scald and SP600125 groups. The rats were inflicted with 30% TBSA full-thickness scald in the latter two groups. Euglycemic-hyperinsulinemic glucose clamp experiment was carried out 4 days after scald. SP600125 was administered to the rats in scald and SP600125 2 hrs before Euglycemic-hyperinsulinemic glucose clamp was performed. Changes in the phospho-Serine307 and phospho-tyrosine of IRS-1 activity, as well as expression of phospho-JNK in muscles were determined.


RESULTS
Euglycemic-Hyperinsulinemic Glucose Clamps experiment showed that the infusion rate of 100 g/L glucose in sham, scald, scald and SP600125 groups were (12. 33 +/-0. 42) , (6. 61 +/-0. 27) , (11. 11 +/-0. 68) mgx kg(-1) x min(-1) , respectively ( P <0.01). The level of IRS-1 Serine307 phosphorylation and JNK activity in muscles were significantly increased, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after scald. Compared with scald group, the level of IRS-1 Serine307 phosphorylation and JNK activity in scald and SP600125 group were decreased but tyrosine phosphorylation was elevated.


CONCLUSIONS
SP600125 can partially ameliorate insulin resistance after scald by inhibition of JNK activation, and decrease the level of IRS-1 phospho-serine307.
Chen
Xin-long
XL
Department of Burns and Plastic Surgery, Affiliated Hospital to Medical College of Chinese People's Armed Police Forces, Tianjin.
Xia
Zhao-fan
ZF
Wei
Duo
D
Ben
Dao-feng
DF
Tang
Hong-tai
HT
Ge
Sheng-de
SD
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D002056:Burns / Q000150:complications / Q000378:metabolism*; D006946:Hyperinsulinism / Q000209:etiology; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000873:Anthracenes; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases