Mitochondrial metabolism and dynamics in pancreatic beta cell glucose sensing.
Mitochondrial metabolism and dynamics in pancreatic beta cell glucose sensing.
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胰腺β细胞葡萄糖传感中的线粒体代谢和动力学。
DOI：
10.1042/bcj20230167
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Soleimanpour,ScottA
中科院分区：
文献类型：
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作者：
Rutter,GuyA;Sidarala,Vaibhav;Kaufman,BrettA;Soleimanpour,ScottA
葡萄糖调节的胰岛素分泌在所有形式的糖尿病中都会出现缺陷。60多年来，糖作用于胰岛内β细胞集合的信号机制仍然是一个活跃的研究领域。在这里，我们首先关注葡萄糖的特殊氧化代谢在葡萄糖检测中的作用，讨论在β细胞中“禁止”包括乳酸脱氢酶（Ldha）和乳酸转运蛋白mct1 / slc16a1在内的基因表达的重要性，以限制葡萄糖的其他代谢命运。接下来，我们将探讨Ca2+对线粒体代谢的调节及其在维持葡萄糖信号传导到胰岛素分泌中的可能作用。最后，我们深入讨论了β细胞中线粒体结构和动力学的重要性，以及它们通过肠促胰岛素激素或线粒体融合的直接调节剂靶向治疗的潜力。这篇综述，以及GAR将于2023年6月在加拿大温哥华举行的胰岛研究小组会议上发表的2023年菲利普·兰德尔爵士讲座，都是为了表彰兰德尔教授和他的同事们对胰岛素分泌调节的理解所做出的基础性的、有时被低估的贡献。
Glucose-regulated insulin secretion becomes defective in all forms of diabetes. The signaling mechanisms through which the sugar acts on the ensemble of beta cells within the islet remain a vigorous area of research after more than 60 years. Here, we focus firstly on the role that the privileged oxidative metabolism of glucose plays in glucose detection, discussing the importance of ‘disallowing' in the beta cell the expression of genes includingLactate dehydrogenase(Ldha) and the lactate transporterMct1/Slc16a1to restrict other metabolic fates for glucose. We next explore the regulation of mitochondrial metabolism by Ca2+and its possible role in sustaining glucose signaling towards insulin secretion. Finally, we discuss in depth the importance of mitochondrial structure and dynamics in the beta cell, and their potential for therapeutic targeting by incretin hormones or direct regulators of mitochondrial fusion. This review, and the 2023 Sir Philip Randle Lecture which GAR will give at the Islet Study Group meeting in Vancouver, Canada in June 2023, honor the foundational, and sometimes under-appreciated, contributions made by Professor Randle and his colleagues towards our understanding of the regulation of insulin secretion.