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Insulin hyperresponsiveness in partially hepatectomized diabetic rats.

机译:部分肝切除的糖尿病大鼠的胰岛素反应过度。

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The present work analyzes the expression of insulin receptors and theirs related intracellular signaling molecules in partially hepatectomized-diabetic rats. Insulin binding through Scatchard analysis was studied using isolated hepatocytes of Control (Sham-operated), Hepatectomized, Diabetic and Diabetic-Hepatectomized male Wistar rats. In a set of in vivo experiments, the levels of alpha subunit of the insulin receptor, the insulin receptor substrate 1 (IRS-1) and the phosphatidylinositol 3-kinase (PI3K) were determined. [3H]-thymidine incorporation into DNA 24 or 48 h after surgery was assessed in all the experimental groups. Scatchard analysis showed that insulin receptor number was increased in diabetic and in hepatectomized rats in the same extent (64%, with respect to Controls). Diabetic-hepatectomized rats showed a dramatic increase of the receptor concentration (400%) and on the affinity constant (532%). Besides, the insulin receptor expression was increased in the treated groups, being the higher values those of the diabetic-hepatectomized rats. IRS-1 and PI3K showed similar increases. DNA synthesis was not impaired by the diabetes state. In conclusion, increased expression of IR and IRS-1 leads to increased association of PI3K in vivo in diabetic regenerating rats. The enhancement of this pathway may reveal an insulin hyperresponsiveness in these animals.
机译:本工作分析了部分肝切除的糖尿病大鼠中胰岛素受体及其相关细胞内信号分子的表达。使用对照(假手术),肝切除,糖尿病和糖尿病肝切除的雄性Wistar大鼠分离的肝细胞,通过Scatchard分析研究了胰岛素结合。在一组体内实验中,确定了胰岛素受体,胰岛素受体底物1(IRS-1)和磷脂酰肌醇3激酶(PI3K)的α亚基的水平。在所有实验组中评估手术后24或48小时[3 H]-胸苷掺入DNA。斯卡查德(Scatchard)分析显示,在糖尿病和肝切除大鼠中,胰岛素受体的数量增加了相同程度(相对于对照组,为64%)。糖尿病肝切除大鼠显示受体浓度(400%)和亲和常数(532%)显着增加。此外,在治疗组中胰岛素受体表达增加,这是糖尿病肝切除大鼠的较高值。 IRS-1和PI3K表现出相似的增长。糖尿病状态不会损害DNA的合成。总之,在糖尿病再生大鼠中,IR和IRS-1的表达增加导致体内PI3K的缔合增加。该途径的增强可能揭示了这些动物的胰岛素超敏反应。

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