Division of Metabolic Diseases, Technische Universität München, 80333 Munich, Germany.
Department of Pharmaceutical Chemistry, Parul Institute of Pharmacy, Parul University, Vadodara 391760, Gujarat, India.
Int J Mol Sci. 2022 Oct 15;23(20):12338. doi: 10.3390/ijms232012338.
Mitochondrial dynamics and bioenergetics are central to glucose-stimulated insulin secretion by pancreatic beta cells. Previously, we demonstrated that a disturbance in glucose-invoked fission impairs insulin secretion by compromising glucose catabolism. Here, we investigated whether the overexpression of mitochondrial fission regulator in MIN6 cells can improve or rescue insulin secretion. Although overexpression slightly improves the triggering mechanism of insulin secretion of the -knockdown cells and has no adverse effects on mitochondrial metabolism in wildtype MIN6 cells, the constitutive presence of unexpectedly impairs insulin content, which leads to a reduction in the absolute values of secreted insulin. Coherent with previous studies in -overexpressing muscle cells, we found that the upregulation of ER stress-related genes (, , and ) possibly impacts insulin production in MIN6 cells. Collectively, we confirm the important role of for the energy-coupling of insulin secretion but unravel off-targets effects by overexpression on insulin content that warrant caution when manipulating in disease therapy.
线粒体动力学和生物能量学对于胰腺β细胞的葡萄糖刺激胰岛素分泌至关重要。先前，我们证明了葡萄糖诱导的分裂紊乱会损害葡萄糖分解代谢，从而影响胰岛素的分泌。在这里，我们研究了过表达线粒体分裂调节剂 在 MIN6 细胞中是否可以改善或挽救胰岛素分泌。尽管 过表达可轻微改善 -敲低细胞胰岛素分泌的触发机制，并且对野生型 MIN6 细胞中的线粒体代谢没有不良影响，但 的组成型存在出人意料地损害了胰岛素含量，导致分泌的胰岛素绝对值减少。与之前在过表达肌肉细胞中的研究一致，我们发现 ER 应激相关基因（、、和 ）的上调可能会影响 MIN6 细胞中的胰岛素生成。总的来说，我们证实了 对于胰岛素分泌的能量偶联的重要作用，但通过 过表达对胰岛素含量产生的脱靶效应值得在疾病治疗中操纵 时谨慎对待。
