Anaplerosis and the associated mitochondrial metabolite transporters generate unique cytosolic metabolic signaling molecules that can regulate insulin release from pancreatic β-cells. It has been shown that mitochondrial metabolites, transported by the citrate carrier (CIC), dicarboxylate carrier (DIC), oxoglutarate carrier (OGC), and mitochondrial pyruvate carrier (MPC) play a vital role in the regulation of glucose-stimulated insulin secretion (GSIS). Metabolomic studies on static and biphasic insulin secretion, suggests that several anaplerotic derived metabolites, including α-ketoglutarate (αKG), are strongly associated with nutrient regulated insulin secretion. Support for a role of αKG in the regulation of insulin secretion comes from studies looking at αKG dependent enzymes, including hypoxia-inducible factor-prolyl hydroxylases (PHDs) in clonal β-cells, and rodent and human islets. This review will focus on the possible link between defective anaplerotic-derived αKG, PHDs, and the development of type 2 diabetes (T2D).

回补和相关的线粒体代谢物转运蛋白产生独特的细胞溶质代谢信号分子，可以调节胰腺 β 细胞的胰岛素释放。已经表明，由柠檬酸盐载体 (CIC)、二羧酸盐载体 (DIC)、酮戊二酸载体 (OGC) 和线粒体丙酮酸载体 (MPC) 运输的线粒体代谢物在调节葡萄糖刺激的胰岛素分泌中起着至关重要的作用。 GSIS）。对静态和双相胰岛素分泌的代谢组学研究表明，包括 α-酮戊二酸 (αKG) 在内的几种回补衍生代谢物与营养调节的胰岛素分泌密切相关。对 αKG 在调节胰岛素分泌中的作用的支持来自对 αKG 依赖性酶的研究，包括克隆 β 细胞、啮齿动物和人类胰岛中的缺氧诱导因子脯氨酰羟化酶 (PHD)。本综述将重点关注有缺陷的回补衍生 αKG、PHD 与 2 型糖尿病 (T2D) 的发展之间的可能联系。