Intramitochondrial loci for the hormonal regulation of hepatic gluconeogenesis.
Intramitochondrial loci for the hormonal regulation of hepatic gluconeogenesis.
复制标题
肝脏糖异生激素调节的线粒体内位点。
DOI：
10.1042/bst0130655
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发表时间：
1985
影响因子：
3.9
通讯作者：
R. Haynes
中科院分区：
文献类型：
--
作者：
R. Haynes
When the mechanisms by which hormones acutely stimulate hepatic gluconeogenesis began to be studied intensely about 20 years ago, the earliest hypotheses of action centred on the mitochondria1 segment of the gluconeogenic pathway. I t was proposed that hormones may accelerate the pyruvate carboxylase reaction by an activation of the carboxylase enzyme through an increase in intramitochondrial acetyl coenzyme A o r by a decrease in mitochondrial Ca”. Considerable research has continued on the control of gluconeogenesis at the level of the mitochondria. Much of this has involved treatment of the intact organism (generally the rat) with hormones or treatment of hepatocyte preparations with hormones followed by isolation of mitochondria and study of these organelles in v i m . A number of mitochondrial functions have been found t o be appreciably stimulated in hepatic mitochondria isolated after hormone treatment, perhaps most notably pyruvate carboxylation and oxidative phosphorylation. The stimulation of enhanced mitochondrial activities is evident 3--4min after hormone treatment and is sensitive t o the same concentrations of hormones that activate gluconeogenesis. Furthermore, after treatment of hepatocytes with hormones, stimulation of pyruvate carboxylation is demonstrable in the cells permeabilized by filipin (Allen et al., 1983). The effects of hormone treatment on mitochondrial function are also demonstrable in crude homogenates of treated liver (Jensen et al., 1983). In spite of these observations, this type of experiment cannot provide entirely convincing evidence that the effects found in isolated mitochondria accurately reflect the events occurring in intact cells, and in recent years there have been several papers in the literature questioning the physiological relevance of studies of mitochondria isolated subsequent t o hormone treatment. Siess et al. (1981) suggested that some or all of the effects found in mitochondria may be artefacts of their preparation. LaNoue and her colleagues reported they were able t o demonstrate neither increases in ‘maximal’ rates of respiration of hepatocytes treated with glucagon nor evidence of an increased ApH across mitochondria1 membranes in situ (LaNoue) e t al., 1984; Strzelecki e t al., 1984). Finally, Groen e t al. (1983) concluded from a study with perifused rat hepatocytes that the stimulation of gluconeogenesis by glucagon can be accounted for almost entirely by inhibition of flux through the pyruvate kmase reaction and that glucagon causes little or n o stimulation of carboxylation of pyruvate.
