Anti-TNF-α antibody alleviates insulin resistance in rats with sepsis-induced stress hyperglycemia
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To explore the effects and mechanisms of anti-tumor necrosis factor-α (TNF-α) antibody on insulin resistance (IR) in rats with sepsis-induced stress hyperglycemia.
The sepsis-induced stress hyperglycemic rat model was constructed by cecal ligation and puncture combined with the intraperitoneal injection of lipopolysaccharide. The rats were randomly divided into six groups: normal control (NC) group, surgical rats (Cntl) group, high-dose anti-TNF-α antibody therapy (TNF, 6 mg/kg) group, low-dose anti-TNF-α antibody therapy (Tnf, 3 mg/kg) group, insulin therapy (INS) group, and INS + Tnf group. The blood glucose and serum insulin concentrations were detected, followed by analysis of intraperitoneal glucose tolerance test (IPGTT) and hyperinsulinemic–euglycemic clamp. Finally, the expression levels of phospho-Akt (p-Akt), Akt, p-mTOR, mTOR, nuclear factor-κB (NFκB), I kappa beta kinase (IKKβ), and suppressor of cytokine signaling (SOCS-3) were detected by western blotting.
There was no significant difference in blood glucose concentrations among these groups, while the serum insulin concentration in TNF and Tnf groups was lower than that in the Cntl group at postoperative 6 h (P < 0.05). IPGTT analysis revealed that blood glucose level was lower in the TNF group than that in the Cntl group (P < 0.05). The glucose infusion rate in the Cntl group was lower than that in the Tnf and TNF groups (P < 0.05). The p-Akt/Akt, p-mTOR/mTOR ratio, and expression levels of NFκB, IKKβ and SOCS-3 were lower in the drug intervention than that in the Cntl group (P < 0.05).
Anti-TNF-α antibody could reduce IR by inhibiting AKt/mTOR signaling pathway and the expression levels of NFκB, IKKβ, and SOCS-3 in rats with sepsis-induced stress hyperglycemia.
KeywordsStress hyperglycemia Insulin sensitivity Anti-TNF-α antibody
Compliance with ethical standards
This study was supported by China Postdoctoral Science Foundation (No. 20080441294).
Conflict of interest
The author declares that they have no conflict of interest.
All the surgical procedures for animal use were approved by the University of Shandong Institutional Animal Care and Use Committee.
No informed consent needed.
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