Mulder Hindrik, Ling Charlotte
Department of Clinical Sciences in Malmö, Unit of Molecular Metabolism, Lund University Diabetes Centre, Clinical Research Center, Malmö University Hospital, Lund University, SE-205 02 Malmö, Sweden.
Mol Cell Endocrinol. 2009 Jan 15;297(1-2):34-40. doi: 10.1016/j.mce.2008.05.015. Epub 2008 Jul 7.
Mitochondrial metabolism controls insulin secretion from the pancreatic beta-cell. Type 2 Diabetes evolves when the beta-cells fail to release appropriate amounts of insulin, causing metabolic dysregulation and hyperglycemia. It is attractive to assume that mitochondrial dysfunction plays a decisive role in these processes. Indeed, while being a rare condition, genetically determined dysfunction of mitochondria causes a Type 2 Diabetes-like syndrome. Here, we review what is known about mitochondrial dysfunction in the beta-cell in Type 2 Diabetes. The focus is on observations in humans but relevant studies in animal models of the disease are discussed. A particular emphasis is placed on changes in metabolic enzymes and function in beta-cell mitochondria and how altered structure of the organelle appears to facilitate its function. These molecular processes are subject to tight genetic as well as epigenetic control. Variations and implications of these mechanisms are reviewed. The emerging picture is that alterations in mitochondria may be a culprit in the pathogenetic processes culminating in Type 2 Diabetes. Such processes may prove to be targets for therapeutic interventions in the disease.
线粒体代谢控制胰腺β细胞的胰岛素分泌。当β细胞无法释放适量胰岛素时，2型糖尿病就会发展，导致代谢失调和高血糖。认为线粒体功能障碍在这些过程中起决定性作用是很有吸引力的。事实上，虽然线粒体的基因决定性功能障碍是一种罕见的情况，但它会导致类似2型糖尿病的综合征。在这里，我们回顾了关于2型糖尿病中β细胞线粒体功能障碍的已知情况。重点是对人类的观察，但也讨论了该疾病动物模型中的相关研究。特别强调了β细胞线粒体中代谢酶和功能的变化，以及细胞器结构的改变如何似乎促进其功能。这些分子过程受到严格的遗传和表观遗传控制。本文综述了这些机制的变异及其影响。新出现的情况是，线粒体的改变可能是导致2型糖尿病的致病过程中的一个罪魁祸首。这些过程可能被证明是该疾病治疗干预的靶点。
