Glucagon stimulation of mitochondrial respiration.
Glucagon stimulation of mitochondrial respiration.
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胰高血糖素刺激线粒体呼吸。
DOI：
10.1016/s0021-9258(19)40904-6
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发表时间：
1975
期刊：
影响因子：
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通讯作者：
Russell K Yamazaki
中科院分区：
文献类型：
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作者：
Russell K Yamazaki
急性胰高血糖素治疗已被发现引起肝脏线粒体呼吸的刺激，通过监测氧摄取极谱测量。在激素处理和线粒体分离后，几种nadd连接底物和琥珀酸盐的状态3呼吸率显著增加。这种刺激不能归因于部分解耦效应，因为状态4呼吸是通过监测摄氧量极谱测量的。状态3呼吸速率有轻微增加或不变。此外，激素治疗后，这些底物的非偶联呼吸速率也受到刺激。另一方面，以抗坏血酸-N，N，N‘，N’-四甲基-对苯二胺为底物的呼吸速率（状态3,4和非偶联）不受胰高血糖素处理的影响。激素刺激的呼吸速率产生了相应的高能量状态的产生速率的增加，这在分离的线粒体对Ca2+摄取的测量中表明。Ca2+的摄取速率通过两种方法进行监测：在CaCl2添加后测量质子喷射的初始速率，并在双波长分光光度计中使用murexide作为指示剂测量悬浮介质中Ca2+的消失。胰高血糖素治疗动物和分离肝线粒体后，琥珀酸盐依赖性Ca2+摄取的初始速率显著刺激。激素治疗对Ca2+摄取的程度或每Ca2+摄取的H+排出的化学计量没有影响。激素对Ca2+运输的影响是在底物诱导的高能态产生的水平上，观察到胰高血糖素治疗对atp依赖性Ca2+摄取没有影响。胰高血糖素诱导的底物代谢酶活性变化被认为不太可能，原因如下：(a)先前发表的数据显示，激素对丙酮酸代谢酶缺乏影响；(b)本研究的数据显示，胰高血糖素治疗对线粒体裂解物中nada -苹果酸脱氢酶的活性没有影响。所有这些观察结果都与胰高血糖素治疗激活线粒体底物运输和/或刺激线粒体电子传递相一致。不管确切的机制是什么，激素治疗的效果是在能量需求增加的时期产生ATP合成和离子泵能力的增加，即糖异生的增加。
Acute glucagon treatment of intact rats has been found to cause a stimulation of hepatic mitochondrial respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with several NAD-linked substrates and succinate were increased significantly after hormonal treatment and isolation of mitochondria. This stimulation cannot be ascribed to a partial uncoupling effect since State 4 respiration as measured by monitoring oxygen uptake polarographically. Rates of State 3 respiration with either slightly increased or unchanged. Furthermore, rates of uncoupled respiration with these substrates were also stimulated after hormonal treatment. On the other hand, respiratory rates (State 3, 4, and uncoupled) with ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine as substrate were unaffected by glucagon treatment. The hormonally stimulated rates of respiration produced a corresponding increase in the rate of generation of high energy state as indicated in measurements of Ca2+ uptake by isolated mitochondria. Rates of Ca2+ uptake were monitored by two methods: measurement of initial rates of proton ejection following CaCl2 additions and measurement of disappearance of Ca2+ from the suspension medium using murexide as indicator in a dual wavelength spectrophotometer. A significant stimulation in the initial rate of succinate-dependent Ca2+ uptake was noted after glucagon treatment of animals and isolation of hepatic mitochondria. No effect of the hormonal treatment was seen on the extent of Ca2+ uptake or the stoichiometry of H+ ejected per Ca2+ taken up. That the hormonal effect on Ca2+ transport is at the level of the substrate-induced generation of high energy state is indicated by the observation that no effect of glucagon treatment is seen on ATP-dependent Ca2+ uptake. Glucagon-induced changes in the activities of substrate-metabolizing enzymes are considered unlikely for the following reasons: (a) previously published data showed a lack of a hormonal effect on pyruvate-metabolizing enzymes and (b) data in this study showing no effect of glucagon treatment on the activity of NAD-malate dehydrogenase as measured in mitochondrial lysates. All of these observations are consistent with either an activation of mitochondrial substrate transport and/or a stimulation of mitochondrial electron transport by glucagon treatment. Regardless of the exact mechanism involved, the effect of the hormonal treatment is to produce an increase in ATP synthetic and ion-pumping capability during a period of increased energy demand, i.e. increased gluconeogenesis.