正常生理和1型糖尿病病理下慢性生长激素刺激对肝脏胰岛素信号的影响

The influence of chronic growth hormone stimulation on hepatic insulin signal under normal physiological and T1DM condition

目的研究1型糖尿病(type 1 diabetes mellitus,T1DM)状态下长期生长激素(growth hormone,GH)治疗对肝脏胰岛素信号的影响及其可能机制。方法用慢性GH注射健康小鼠与链尿佐菌素(STZ)诱导的T1DM小鼠,Western blotting检测Akt和PTEN等。结果在健康Balb/c小鼠,GH慢性刺激可抑制肝内胰岛素信号通路分子Akt磷酸化(P<0.05),而该信号通途的负调控分子PTEN表达则显著增加(P<0.05);在T1DM C57BL/6小鼠,慢性GH刺激同样抑制肝内Akt磷酸化(P<0.05),而PTEN表达水平则无显著改变(P>0.05)。同时检测胰岛素信号的另一个负调节因子p85调节亚基,当经慢性GH刺激后,其表达水平在两种小鼠中均没有变化(P>0.05)。结论长期使用GH治疗可以抑制肝脏胰岛素信号,其机制涉及PTEN表达的升高,但其病理状态下的机制则不同。

Objective To research the influence and possible mechanism of chronic growth hormone （GH） on he- patic insulin signal under type 1 diabetes mellitus （T1DM） condition. Methods Chronic GH induced insulin resistance in mice with T1 DM which induced by Streptozoein （STZ）. Then hepatic Akt phosphorylation and PTEN were detected by Western blotting. Results In healthy mice, chronic GH treatment inhibited hepatic p-Akt. PTEN expression was in- creased （P 〈 0.05 ）. In T1DM mice, chronic GH caused similar inhibition of p-Akt （ P 〈 0.05 ）, but PTEN expression did not change （P 〉 0.05）. The p85 expression did not change in both health and T1 DM mice after chronic GH treat- ment （P 〉 0.05）. Conclusion Long-term use of chronic GH treatment can inhibite hepatic insulin signaling and the mechanism involves the increasing PTEN expression, but the underlying mechanism is different in pathological status.