Sebokova E, Gasperikova D, Ouwens M, Dorrestijn J, Eckel J, Maasen A, Klimes I
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
Endocr Regul. 1999 Jun;33(2):49-54.
To study the regulation of phosphatidylinositol (PI) 3-kinase by insulin in vivo in hereditary hypertriglyceridemic and insulin resistant rat (hHTg).
Total and insulin receptor substrate-1 (IRS-1) associated PI 3-kinase activities were measured in skeletal muscles and adipose tissue after an intense insulin induced glucose utilization as accomplished by 90 min euglycemic hyperinsulinemic clamp.
In quadriceps femoris muscle, no stimulation of total or IRS-1 associated PI 3-kinase activities was found after hyperinsulinemia in both hHTg and control rats. In contrast, in soleus muscle of control rats total PI 3-kinase activity was stimulated by insulin (P<0.001), while any such effect was not found in hHTg rats. IRS-1 associated PI 3-kinase activity in soleus muscle was significantly decreased in hHTg rats when compared to control rats (P<0.001), but was not affected by insulin. In white adipose tissue (WAT), both the total (P<0.05) and IRS-1 associated PI 3-kinase activities (P<0.001) were increased after 90 min hyperinsulinemia in control animals but not in hHTg animals.
Long-term activation of PI 3-kinase activity by insulin in vivo involves IRS-1 in white adipose tissue, but not in skeletal muscle which implies tissue specificity. The impairment in the PI 3-kinase activation by insulin in hHTg rats may participate in insulin resistance of these animals.
研究遗传性高甘油三酯血症和胰岛素抵抗大鼠（hHTg）体内胰岛素对磷脂酰肌醇（PI）3激酶的调节作用。
通过90分钟的正常血糖高胰岛素钳夹技术实现胰岛素诱导的强烈葡萄糖利用后，测量骨骼肌和脂肪组织中总的及与胰岛素受体底物-1（IRS-1）相关的PI 3激酶活性。
在股四头肌中，hHTg大鼠和对照大鼠在高胰岛素血症后均未发现总的或与IRS-1相关的PI 3激酶活性受到刺激。相比之下，对照大鼠比目鱼肌中的总PI 3激酶活性受到胰岛素刺激（P<0.001），而hHTg大鼠未发现这种作用。与对照大鼠相比，hHTg大鼠比目鱼肌中与IRS-1相关的PI 3激酶活性显著降低（P<0.001），但不受胰岛素影响。在白色脂肪组织（WAT）中，对照动物在90分钟高胰岛素血症后总的（P<0.05）及与IRS-1相关的PI 3激酶活性（P<0.001）均升高，而hHTg动物则未升高。
胰岛素在体内对PI 3激酶活性的长期激活在白色脂肪组织中涉及IRS-1，但在骨骼肌中不涉及，这意味着存在组织特异性。hHTg大鼠中胰岛素对PI 3激酶激活的损害可能参与了这些动物的胰岛素抵抗。
