Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Arch Biochem Biophys. 2010 Jul;499(1-2):62-8. doi: 10.1016/j.abb.2010.05.007. Epub 2010 May 9.
Succinyl-CoA:3-ketoacid-CoA transferase (SCOT) is a mitochondrial enzyme that catalyzes the reversible transfer of coenzyme-A from acetoacetyl-CoA to succinate to form acetoacetate and succinyl-CoA. mRNAs of SCOT and ATP citrate lyase were decreased 55% and 58% and enzyme activities were decreased >70% in pancreatic islets of the GK rat, a model of type 2 diabetes. INS-1 832/13 cells were transfected with shRNAs targeting SCOT mRNA to generate cell lines with reduced SCOT activity. Two cell lines with >70% knockdown of SCOT activity showed >70% reduction in glucose- or methyl succinate-plus-beta-hydroxybutyrate-stimulated insulin release. Less inhibition of insulin release was observed with two cell lines with less knockdown of SCOT. Previous studies showed knockdown of ATP citrate lyase in INS-1 832/13 cells does not lower insulin release. The results further support work that suggests mitochondrial pathways involving SCOT which supply acetoacetate for export to the cytosol are important for insulin secretion.
琥珀酰辅酶 A:3-酮酸辅酶 A 转移酶 (SCOT) 是一种线粒体酶，可催化辅酶 A 从乙酰乙酰辅酶 A 可逆转移到琥珀酸，形成乙酰乙酸和琥珀酰辅酶 A。2 型糖尿病模型 GK 大鼠的胰岛中，SCOT 和 ATP 柠檬酸裂解酶的 mRNA 降低了 55%和 58%，酶活性降低了>70%。INS-1 832/13 细胞用靶向 SCOT mRNA 的 shRNA 转染，产生 SCOT 活性降低的细胞系。两种 SCOT 活性降低>70%的细胞系，葡萄糖或甲基琥珀酸加β-羟基丁酸刺激胰岛素释放的抑制作用>70%。两种 SCOT 敲低程度较低的细胞系观察到的胰岛素释放抑制作用较小。先前的研究表明，INS-1 832/13 细胞中 ATP 柠檬酸裂解酶的敲低不会降低胰岛素释放。结果进一步支持了以下工作，即涉及为细胞溶质输出提供乙酰乙酸的 SCOT 的线粒体途径对胰岛素分泌很重要。
