应激信号通路参与非糖尿病腹膜透析患者的胰岛素抵抗

Stress signaling pathway involved in insulin resistance induced by peritoneal dialysis in non diabetic patients

目的 探讨非糖尿病腹膜透析患者的胰岛素抵抗与应激敏感性激酶即c-Jun氨基末端激酶(JNK)及核因子κB抑制物激酶(IKK)的关系.方法 选择非糖尿病腹膜透析时间＞3个月的连续性不卧床腹膜透析(CAPD)患者51例,健康对照组20名.测定患者空腹血糖、空腹胰岛素并计算胰岛素抵抗指数(IR),按照该指数将病例分为高IR组和低IR组.采用酶联免疫吸附测定法检测3组血浆的JNK及IKK活性.结果 非糖尿病腹膜透析患者低IR组和高IR组的稳态胰岛素抵抗指数(HOMA-IR)分别为3.57±1.46和5.01±1.40,均高于健康对照组(2.37±1.62) (F=18.17,P=0.000).高IR组的JNK及IKK活性高于低IR组[JNK:(77.54±10.01) μg/L与(56.33±9.72) μg/L,P＜0.01),IKK:(321.69±21.23) μg/L与(225.12±19.43) μg/L,P＜0.01],且两组均高于健康对照组[JNK:(21.13±4.17)μg/L,IKK:(104.01±14.22) μg/L;P均＜0.01].相关分析结果表明,非糖尿病腹膜透析患者的HOMA-IR分别与JNK和IKK活性呈正相关(r=0.67,P＜0.01和r=0.61,P＜0.01).结论 非糖尿病腹膜透析患者存在胰岛素抵抗,且与血浆JNK及IKK的活性呈正相关,提示应激信号通路可能参与了非糖尿病腹膜透析患者的胰岛素抵抗.

Objective To investigate the relationship between stress kinases (c-Jun N-terminal kinase (JNK) and nuclear factor kappa B inhibitor kinase(IKK)) and insulin resistance induced by peritoneal dialysis in non diabetic patients.Methods Fifty-one non diabetic patients were selected as our subjects,who had received continuous ambulatory peritoneal dialysis (CAPD) at least for 3 months,and were divided into high insulin resistance(IR) group and low IR group according to IR index.Meanwhile,20 healthy people were served as our control group.The level of glucose and insulin were detected for calculating HOMA-IR which was used for evaluating the degree of insulin resistance.The activity of plasma JNK and IKK of all subjects were detected by ELISA.Results Compared with control (2.37 ± 1.62),the HOMA-IR of patients in low-IR group and high-IR group were higher(3.57 ± 0.46 and 5.01 ± 1.40 respectively; F =18.17,P =0.000).Plasma JNK and IKK activities in high-IR group were (77.54 ± 10.01) μg/L and (321.69 ±21.23) μg/L,higher than that of low-IR group((56.33 ±9.72) μg/L,(225.12 ± 19.43) μg/L respectively,P ＜0.01).The activity of plasma JNK and IKK in all patients were higher than in controls((21.13 ±4.17) μg/L,(104.01 ± 14.22) μg/L,P ＜0.01).The correlation analysis results indicated that there were the positive correlation between the insulin resistance state and the activity of plasma JNK or IKK in non diabetic patients treated with CAPD (r =0.67,P ＜ 0.01 and r =0.61,P ＜ 0.01).Conclusion Insulin resistance occur in nondiabetic patients with CAPD and correlated with the plasma JNK and IKK activity,which suggest a role of stress signal pathway in insulin resistance caused by peritoneal dialysis.