首页> 外文期刊>The Journal of laboratory and clinical medicine >Effects of glucagon on glycogenolysis and gluconeogenesis are region-specific in periportal and perivenous hepatocytes.
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Effects of glucagon on glycogenolysis and gluconeogenesis are region-specific in periportal and perivenous hepatocytes.

机译:胰高血糖素对门静脉和静脉肝细胞的糖原分解和糖异生作用是区域特异性的。

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It has been established, mainly by histochemical and immunohistochemical studies, that liver cells are functionally heterogeneous, with periportal hepatocytes (PPHs) being predominantly gluconeogenic and perivenous hepatocytes (PVHs) being glycolytic. We therefore investigated the region-specific functional effects of glucagon on glycogenolysis and gluconeogenesis in isolated PPHs and PVHs prepared by the digitonin-collagenase method. BB rats, a model of insulin-dependent diabetes, were used to study the region-specific heterogeneity of gluconeogenesis in the diabetic state. Although glycogen content was not different between PVHs and PPHs in rats fed the normal diet, basal glucose release was 1.37 times greater in PVHs than in PPHs (P <.05). The increase in glucose release stimulated by 0.01 to 0.1 nmol/L glucagon was 1.52 times greater in PVHs than in PPHs (P < .05), whereas no differences were seen in response to 1 to 100 nmol/L glucagon. Glucose release from gluconeogenic substrates was 1.57 times greater in the PPHs than in the PVHs of fasted normal rats (P < .05), whereas the increase in gluconeogenesis produced by glucagon was not different between PPHs and PVHs. The glucagon-binding capacity, the cAMP release, and the increase in intracellular Ca2+ stimulated by glucagon were not different between PPHs and PVHs in the fed or fasted states. Gluconeogenesis from gluconeogenic substrates was 1.52 times greater in the PPHs than in the PVHs of fasted nondiabetic BB rats (P < .05). After the development of diabetes, the gluconeogenic capacity in PVHs increased to the level observed in PPHs, but that in PPHs did not change. Thus there was no difference in gluconeogenesis between the PPHs and PVHs of diabetic BB rats. In both the PPHs and PVHs of diabetic BB rats, the 0.01 to 100 nmol/L glucagon-induced increase in gluconeogenesis was greater than that in PPHs from nondiabetic BB rats (2.30 and 3.07 times, P < .01, respectively). We conclude that PPHs and PVHs of normal rat liver express region-specific differences in their glycogenolytic and gluconeogenic responses to glucagon. In diabetic BB rats, the difference in the gluconeogenic capacity between PPHs and PVHs disappeared, whereas glucagon-induced gluconeogenesis was enhanced.
机译:主要通过组织化学和免疫组织化学研究已经确定,肝细胞在功能上是异质的,其中门静脉肝细胞(PPH)主要是糖异生,而静脉肝细胞(PVH)是糖酵解的。因此,我们调查了由洋地黄菌素-胶原酶方法制备的分离的PPH和PVH中胰高血糖素对糖原分解和糖异生的区域特异性功能作用。 BB大鼠是胰岛素依赖型糖尿病的模型,用于研究糖尿病状态下糖异生的区域特异性异质性。尽管正常饮食的大鼠中PVH和PPH之间的糖原含量没有差异,但是PVH中的基础葡萄糖释放量是PPH中的1.37倍(P <.05)。在PVHs中,0.01至0.1 nmol / L胰高血糖素刺激的葡萄糖释放增加比PPHs高1.52倍(P <.05),而对1至100 nmol / L胰高血糖素的反应未见差异。在PPH中,葡萄糖从糖异生底物释放的速度是正常禁食正常大鼠PVH中的1.57倍(P <.05),而在PPH和PVH中,胰高血糖素产生的糖原异生的增加没有差异。 PPH和PVH在进食或禁食状态下的胰高血糖素结合能力,cAMP释放以及胰高血糖素刺激的细胞内Ca2 +的增加没有差异。在PPH中,来自糖异生底物的糖异生比禁食的非糖尿病BB大鼠的PVH高1.52倍(P <.05)。糖尿病发生后,PVHs的糖原异生能力增加到了PPHs中观察到的水平,但PPHs中没有。因此,糖尿病BB大鼠的PPH和PVH之间的糖异生没有差异。在糖尿病BB大鼠的PPH和PVH中,胰高血糖素诱导的0.01至100 nmol / L胰高血糖素诱导的糖异生增加大于非糖尿病BB大鼠的PPH(分别为2.30和3.07倍,P <.01)。我们得出结论,正常大鼠肝脏的PPH和PVH在其对胰高血糖素的糖原分解和糖异生反应中表达区域特异性差异。在糖尿病BB大鼠中,PPH和PVH之间的糖原异生能力差异消失,而胰高血糖素诱导的糖原异生增强。

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