Effect of early insulin therapy on nuclear factor kappaB and cytokine gene expressions in the liver and skeletal muscle of high-fat diet, streptozotocin-treated diabetic rats.
To clarify the effect of early insulin therapy on nuclear factor kappaB (NFkappaB) pathway and inflammatory cytokine responses in the liver and skeletal muscle in type 2 diabetes. High-fat diet and low dose streptozotocin (STZ) induced diabetic rats were given NPH insulin or gliclazide for 3 weeks initiated at the 3rd day after STZ injection as early treatment and NPH for 3 weeks at 1 month as late treatment. Intraperitoneal glucose tolerance test (IPGTT) was performed at 3rd day after the end of treatment. Early interventions caused a decrease in glucose-insulin index in IPGTT, promoted glucose transporter 4 (Glut4) gene and protein expressions in muscle and reduced phosphoenolpyruvate carboxykinase (PEPCK) protein levels in the liver. There was an increase in inhibitor kappaB (IkappaBalpha) protein and a decrease in NFkappaB p65 DNA binding activity. A decreased level in mRNAs encoding tumor necrosis factor (TNF)alpha in the liver and muscle and interleukin (IL)-1beta in the liver were observed. Our results suggested that early insulin treatment inhibits NFkappaB activity and inflammatory cytokine responses in the liver and skeletal muscle that were involved in the amelioration of insulin resistance in type 2 diabetic rats.
Bi
Y
Y
Department of Endocrinology, The Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangzhou, 510630, China.
Sun
W P
WP
Chen
X
X
Li
M
M
Liang
H
H
Cai
M Y
MY
Zhu
Y H
YH
He
X Y
XY
Xu
F
F
Weng
J P
JP
D000818:Animals; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004036:Diet, Atherogenic; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D013997:Time Factors
D001786:Blood Glucose; D016207:Cytokines; D007004:Hypoglycemic Agents; D007328:Insulin; D053583:Interleukin-1beta; D016328:NF-kappa B; D013311:Streptozocin