CAJ | 학술논문

目的探讨TNF-α诱导的胰岛素抵抗(IR)小鼠胰岛素敏感性及糖脂代谢的变化. 方法 23只健康雄性C57BL/6J小鼠随机分为4组:高剂量(H)组、中剂量(M)组、低剂量(L)组分别给予腹腔注射6、3、1μg·kg-1·d-1的TNF-α,正常对照(NC)组注射等体积的生理盐水,共7天.采用静脉葡萄糖耐量试验(IVGTT)和3-[3H]葡萄糖为示踪剂的扩展胰岛素钳夹技术,评价小鼠胰岛素敏感性和糖脂代谢的变化.结果 TNF-α处理后,小鼠FBG、血浆胰岛素(Ins)和FFA水平均增高,且H组明显高于NC、M和L组.IVGTT结果显示H组糖耐量减低,Ins释放水平明显高于其他组. 在胰岛素钳夹术中,H组基础葡萄糖清除率(GDR)和肝糖输出率(HGP)明显高于NC组(P<0.01).在钳夹稳态时,H组血浆Ins水平明显高于NC组 (P<0.01),Ins对FFA的抑制作用较NC组明显降低(P<0.01), H组葡萄糖输注率(GIR)明显低于NC组(P<0.01);钳夹稳态时小鼠GDR明显增加,但H组GDR的增加仍明显低于NC组(P<0.01);钳夹结束时,NC组HGP被完全抑制,而H组仅被抑制59%.结论高剂量TNF-α(6μg·kg-1·d-1)处理可导致小鼠糖脂代谢紊乱以及肝和外周组织的IR.
목적 탐토TNF-α유도적이도소저항(IR)소서이도소민감성급당지대사적변화. 방법 23지건강웅성C57BL/6J소서수궤분위4조:고제량(H)조、중제량(M)조、저제량(L)조분별급여복강주사6、3、1μg·kg-1·d-1적TNF-α,정상대조(NC)조주사등체적적생리염수,공7천.채용정맥포도당내량시험(IVGTT)화3-[3H]포도당위시종제적확전이도소겸협기술,평개소서이도소민감성화당지대사적변화.결과 TNF-α처리후,소서FBG、혈장이도소(Ins)화FFA수평균증고,차H조명현고우NC、M화L조.IVGTT결과현시H조당내량감저,Ins석방수평명현고우기타조. 재이도소겸협술중,H조기출포도당청제솔(GDR)화간당수출솔(HGP)명현고우NC조(P<0.01).재겸협은태시,H조혈장Ins수평명현고우NC조 (P<0.01),Ins대FFA적억제작용교NC조명현강저(P<0.01), H조포도당수주솔(GIR)명현저우NC조(P<0.01);겸협은태시소서GDR명현증가,단H조GDR적증가잉명현저우NC조(P<0.01);겸협결속시,NC조HGP피완전억제,이H조부피억제59%.결론 고제량TNF-α(6μg·kg-1·d-1)처리가도치소서당지대사문란이급간화외주조직적IR.
Objective To investigate the effects of tumor necrosis factor-alpha (TNF-α) on insulin sensitivity and glucose-lipid metabolism in TNF-α-induced IR mice. Methods Male C57BL/6J mice were given an intraperitoneal injection of TNF-α (H group,6μg/kg; M group,3μg/kg; L group,1μg/kg;twice daily) and saline (NC group) for 7 days. The plasma glucose and insulin were assayed during intravenous glucose tolerance test (IVGTT) and hyperinsulinemic-euglycemic clamp combined with 3-[3H] glucose as a tracer was carried out. Results After TNF-α treatment,fasting blood glucose (FBG),plasma insulin and free fatty acids (FFA) were significantly elevated in H group compared with NC,L and M groups (P<0.01 and P<0.05,respectively). There was a lower glucose tolerance in H group versus other three groups during IVGTT. The insulin release by glucose stimulation was higher in H group versus NC and L groups (P<0.01 and P<0.05). Basal glucose disappearance rate (GDR) and hepatic glucose production (HGP) were significantly increased in H group compared with NC group (P<0.01). During the steady-state of clamp,plasma insulin levels were significantly increased in H group versus NC group (341.7±17.7 vs 84.7±5.5mU/L,P<0.01). The suppressive effect of insulin on FFA was significantly blunted in H group compared with NC group (0.82±0.03 vs 0.43±0.07mmol/L,P<0.01). Steady-state glucose infusion rate (GIR) was significantly decreased in H group compared with NC group (39.1±2.3 vs 54.2±2.2 mg·kg-1·min-1,P<0.01). Although GDR was increased in both group,but it was still lower in H group than in control group(47.9±0.8 vs 53.9±2.0 mg.kg-1.min-1,P<0.01).As compared with baseline,HGP in the controls was almost completely suppressed during steady state of clamp,but in H group suppressed by approximately 41%. Conclusions High-dose TNF-α treatment induces the abnormality of glucose-lipid metabolism and the insulin resistance of hepatic and peripheral tissue in mice