[Effect of early insulin therapy on nuclear factor-kappaB inflammatory pathway in liver of diabetic rat].
OBJECTIVE
To investigate the effect of early insulin therapy on NF-kappaB pathway and inflammatory cytokine responses in liver of diabetic rat.


METHODS
NF-kappaB p65 DNA binding was assayed with ELISA-based assay kit, cytokine gene expressions were quantified with real-time PCR and phosphoenolpyruvate carboxykinase (PEPCK), NF-kappaB and inhibitor kappaB (IkappaBalpha) protein levels were assayed with Western blot. Results Compared with control, hepatic PEPCK protein level in the untreated diabetic rat increased by 40%. Early insulin and gliclazide treatment normalized PEPCK protein level. The abundance of IkappaBalpha protein was significantly decreased and nuclear NF-kappaB p65 DNA binding activity was increased in untreated diabetic rats. IkappaBalpha protein content increased and NF-kappaB p65 DNA binding decreased during early intervention treatment. mRNAs encoding IL-1beta and TNFalpha were increased, which were reduced to normal levels after insulin and gliclazide treatment.


CONCLUSIONS
It is suggested that early insulin treatment inhibits NF-kappaB activity and inflammatory cytokine responses in liver that are involved in the amelioration of insulin resistance in diabetic rats. Such results might be due to indirect antiinflammatory effects of insulin thus relieving glucotoxicity and lipotoxicity in peripheral tissues.
Bi
Yan
Y
Department of Endocrinology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Meng-yin
Cai
C
Liang
Hua
H
Sun
Wei-ping
WP
Chen
Xiang
X
Zhu
Yan-hua
YH
He
Xiao-ying
XY
Yu
Qiu-qiong
QQ
Li
Ming
M
Weng
Jian-ping
JP
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020672:I-kappa B Proteins; D007328:Insulin; D053583:Interleukin-1beta; C000606206:Nfkbia protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D019764:Phosphoenolpyruvate Carboxykinase (ATP)