在肝细胞中将葡萄糖转化为糖原的过程中，丙酮酸循环对[6-3H]葡萄糖损失的贡献：胰岛素、葡萄糖及肝细胞腺泡来源的影响。

The contribution of pyruvate cycling to loss of [6-3H]glucose during conversion of glucose to glycogen in hepatocytes: effects of insulin, glucose and acinar origin of hepatocytes.

作者信息

Agius L, Tosh D, Peak M

机构信息

Department of Medicine, The Medical School, University of Newcastle upon Tyne, U.K.

出版信息

Biochem J. 1993 Jan 1;289 ( Pt 1)(Pt 1):255-62. doi: 10.1042/bj2890255.

DOI:10.1042/bj2890255

PMID:8380985

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1132158/

Abstract

During conversion of [6-3H,U-14C]glucose to glycogen in liver, loss of 6-3H can occur either by cycling via pyruvate (between glycolysis and gluconeogenesis) or by other mechanisms. We used mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, to determine the extent to which pyruvate cycling contributes to loss of 6-3H during glucose conversion to glycogen in hepatocytes. 2. Mercaptopicolinate increased the 3H/14C ratio in glycogen during incubation of rat, guinea pig, pig and human hepatocytes with [6-3H,U-14C]glucose. The increase in the 3H/14C ratio in glycogen caused by mercaptopicolinate was greater in periportal than in perivenous rat hepatocytes, indicating that cycling of glucose via pyruvate is more prominent in cells with a higher gluconeogenic relative to glycolytic capacity. 3. The effect of mercaptopicolinate on the 3H/14C ratio in glycogen was observed both in the absence and in the presence of insulin, indicating that stimulation of glycogen synthesis by insulin is not associated with inhibition of pyruvate cycling. In rat and guinea pig but not in pig hepatocytes, the effects of mercaptopicolinate on the 3H/14C ratio in glycogen were greater at 10-15 mM glucose than at 30 mM glucose, suggesting diminished cycling via pyruvate at high glucose concentrations. 4. Insulin increased the loss of 6-3H during stimulation of conversion of glucose to glycogen in hepatocytes from all species. This was due in part to an increase in pyruvate cycling and in part to other mechanisms that are not inhibited by mercaptopicolinate. 5. These results suggest that pyruvate cycling is a significant, but not exclusive, component of the loss of 6-3H in the hepatocyte during glucose conversion to glycogen. The extent of pyruvate cycling is dependent on the acinar origin of the hepatocytes and on the glucose concentration and presence of insulin.

摘要

在肝脏中[6 - ³H，U - ¹⁴C]葡萄糖转化为糖原的过程中，6 - ³H的丢失可能通过丙酮酸循环（在糖酵解和糖异生之间）或其他机制发生。我们使用磷酸烯醇式丙酮酸羧激酶抑制剂巯基吡啶甲酸盐，来确定丙酮酸循环在肝细胞中葡萄糖转化为糖原过程中对6 - ³H丢失的贡献程度。2. 在大鼠、豚鼠、猪和人肝细胞与[6 - ³H，U - ¹⁴C]葡萄糖一起孵育期间，巯基吡啶甲酸盐增加了糖原中的³H/¹⁴C比值。巯基吡啶甲酸盐引起的糖原中³H/¹⁴C比值的增加在大鼠门静脉周围肝细胞中比在肝静脉周围肝细胞中更大，这表明相对于糖酵解能力，糖异生能力较高的细胞中，通过丙酮酸的葡萄糖循环更为显著。3. 在有胰岛素和无胰岛素的情况下，均观察到巯基吡啶甲酸盐对糖原中³H/¹⁴C比值的影响，这表明胰岛素对糖原合成的刺激与丙酮酸循环的抑制无关。在大鼠和豚鼠肝细胞中，但在猪肝细胞中未观察到，巯基吡啶甲酸盐对糖原中³H/¹⁴C比值的影响在10 - 15 mM葡萄糖浓度下比在30 mM葡萄糖浓度下更大，这表明在高葡萄糖浓度下通过丙酮酸的循环减少。4. 在所有物种的肝细胞中，胰岛素在刺激葡萄糖转化为糖原的过程中增加了6 - ³H的丢失。这部分是由于丙酮酸循环增加，部分是由于不受巯基吡啶甲酸盐抑制的其他机制。5. 这些结果表明，丙酮酸循环是肝细胞在葡萄糖转化为糖原过程中6 - ³H丢失的一个重要但非唯一的组成部分。丙酮酸循环的程度取决于肝细胞的腺泡来源、葡萄糖浓度和胰岛素的存在。