Insulin action and binding in isolated hepatocytes from fasted, streptozotocin-diabetic, and older, spontaneously obese rats.
Insulin action and binding in isolated hepatocytes from fasted, streptozotocin-diabetic, and older, spontaneously obese rats.
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禁食、链脲佐菌素糖尿病大鼠和老年自发性肥胖大鼠分离肝细胞中的胰岛素作用和结合。
DOI：
10.1042/bj1880839
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
Amatruda,JM
中科院分区：
文献类型：
--
作者：
Cech,JM;FreemanJr,RB;Caro,JF;Amatruda,JM
在年轻对照大鼠、老年自发性肥胖大鼠、72小时饥饿大鼠和非酮症链脲霉素糖尿病大鼠的分离肝细胞中，测量了胰岛素结合以及基础和胰岛素刺激下α-氨基异丁酸的摄取。从老年自发性肥胖大鼠分离的肝细胞在大小、最大胰岛素反应性、胰岛素刺激的氨基异丁酸摄取的剂量-反应关系以及胰岛素受体的数量和亲和力方面与年轻的小鼠相似。禁食72小时的大鼠的肝细胞与年轻对照动物的肝细胞具有相似的胰岛素受体数量，但肝细胞明显更小，对氨基异丁酸盐摄取的基础率更高，并且在0.1mm时对氨基异丁酸盐的最大胰岛素刺激摄取具有胰岛素抵抗性。由于对胰岛素的最大反应降低，引起氨基异丁酸摄取半最大反应的胰岛素浓度降低。来自糖尿病动物的肝细胞，如来自饥饿大鼠的肝细胞，具有显著更高的氨基异丁酸摄取的基础率；虽然最大绝对胰岛素反应与对照细胞相同，但百分比反应较小。这些细胞比对照细胞结合更多的胰岛素。胰岛素结合的增加反映在胰岛素刺激的氨基异丁酸盐摄取的剂量-反应曲线的左移。这些研究表明，老年肥胖大鼠肝细胞对氨基异丁酸盐的摄取没有胰岛素抵抗。此外，在饥饿大鼠肝细胞中观察到的胰岛素抵抗发生在每单位表面积受体数量增加的情况下，这不能用胰岛素与其受体之间相互作用的改变来解释。然而，单位表面积的胰岛素结合增强反映在胰岛素的剂量-反应曲线的左移上。糖尿病动物的肝细胞也是如此，其中每个细胞的胰岛素结合增加。
Insulin binding and basal and insulin-stimulated uptake of α-aminoisobutyric acid were measured in isolated hepatocytes from young control rats as well as from older spontaneously obese, 72h-starved, and nonketotic streptozotocin-diabetic rats. Isolated hepatocytes from older spontaneously obese rats are similar to those from younger smaller rats in size, maximal insulin responsiveness, the dose–response relationship for insulin-stimulated aminoisobutyrate uptake, and the number and affinity of insulin receptors. Hepatocytes from 72h-fasted rats have similar numbers of insulin receptors per cell as cells from young control animals, but are significantly smaller, have an enhanced basal rate of aminoisobutyrate uptake, and are insulin resistant with regard to maximal insulin-stimulated uptake of aminoisobutyrate at 0.1mm-aminoisobutyrate. Because of the decreased maximal response to insulin, the concentration of insulin that elicits a half-maximal response of aminoisobutyrate uptake is decreased. Hepatocytes from diabetic animals, like those from starved rats, have significantly greater basal rates of aminoisobutyrate uptake; whereas the maximal absolute insulin response is the same as control cells, the percentage response is smaller. These cells bind significantly more insulin than do control cells. The increase in insulin binding is reflected in a shift to the left of the dose–response curve for insulin-stimulated uptake of aminoisobutyrate. These studies indicate that there is no insulin resistance with regard to uptake of aminoisobutyrate in hepatocytes from older obese rats. Furthermore, the insulin resistance observed in hepatocytes from starved rats occurs despite an increase in the number of receptors per unit surface area and cannot be explained by alterations in the interaction between insulin and its receptor. The enhanced insulin binding per unit surface area, however, is reflected in the shift to the left of the dose–response curve for insulin. This is also true for hepatocytes from diabetic animals, in which insulin binding per cell is increased.