Metabolic oscillations in β-cells
Metabolic oscillations in β-cells
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DOI：
10.2337/diabetes.51.2007.s152
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发表时间：
2002-02-01
期刊：
影响因子：
7.7
通讯作者：
Jung, SK
中科院分区：
文献类型：
--
作者：
Kennedy, RT;Kauri, LM;Jung, SK
尽管振荡胰岛素分泌的机制仍然未知，但已经提出了几种模型来解释它们是否涉及β细胞中代谢振荡的产生。包括耗氧量、葡萄糖消耗、NADH 和 ATP/ADP 比率测量在内的证据已经积累起来，支持 β 细胞中的能量代谢可能振荡的假设。在进行同时测量的情况下，这些振荡与细胞内 [Ca2+] 和胰岛素分泌的振荡密切相关。大量证据表明，Ca2+ 进入细胞可以积极和消极地调节新陈代谢。 Ca2+ 的主要积极作用是增加耗氧量，据信与线粒体脱氢酶的激活有关。 Ca2+ 的负反馈包括葡萄糖消耗的减少和线粒体膜电位的降低。 Ca2+ 还通过增加 ATP 的消耗来提供负反馈。 Ca2+ 提供的负反馈提供了一种产生振荡的机制，该机制基于以下模型：葡萄糖刺激 ATP/ADP 比率上升，从而关闭 ATP 敏感的 K+ (K-ATP) 通道，从而使细胞膜去极化并允许 Ca(2+) 通过电压敏感通道进入。 Ca2+ 的进入降低了 ATP/ADP 比率并允许重新打开 KATP 通道。糖尿病 51（增补 1）：S152-5161，2002。
Whereas the mechanisms underlying oscillatory insulin secretion remain unknown, several models have been advanced to explain if they involve generation of metabolic oscillations in beta-cells. Evidence, including measurements of oxygen consumption, glucose consumption, NADH, and ATP/ADP ratio, has accumulated to support the hypothesis that energy metabolism in beta-cells can oscillate. Where simultaneous measurements have been made, these oscillations are well correlated with oscillations in intracellular [Ca2+] and insulin secretion. Considerable evidence has been accumulated to suggest that entry of Ca2+ into cells can modulate metabolism both positively and negatively. The main positive effect of Ca2+ is an increase in oxygen consumption, believed to involve activation of mitochondrial dehydrogenases. Negative feedback by Ca2+ includes decreases in glucose consumption and decreases in the mitochondrial membrane potential. Ca2+ also provides negative feedback by increasing consumption of ATP. The negative feedback provided by Ca2+ provides a mechanism for generating oscillations based on a model in which glucose stimulates a rise in ATP/ADP ratio that closes ATP-sensitive K+ (K-ATP) channels, thus depolarizing the cell membrane and allowing Ca(2+)entry through voltage-sensitive channels. Ca2+ entry reduces the ATP/ ADP ratio and allows reopening of the KATP channel. Diabetes 51 (Suppl. 1):S152-5161, 2002.