Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Mediators Inflamm. 2013;2013:920214. doi: 10.1155/2013/920214. Epub 2013 May 21.
Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1) severe, non-syndromic obesity, (2) pancreatic beta cell forms of early-onset diabetes, and (3) severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted.
鉴定由单个基因突变引起的罕见人类代谢紊乱，不仅使此类患者的诊断和临床管理得到改善，而且还深入了解了日益流行的代谢综合征的病理生理学的关键生物学机制。胰岛素抵抗和 2 型糖尿病与肥胖有关，其诱因是热量摄入过多和体力活动减少。然而，代谢综合征病因中的关键事件很难从代偿作用和伴随现象中区分出来。这篇综述概述了三种类型的人类单基因疾病，它们导致（1）严重的、非综合征性肥胖，（2）早发性糖尿病的胰腺β细胞形式，和（3）严重的胰岛素抵抗。在这些由于单一基因缺陷导致其代谢紊乱加剧的患者中，主要缺陷是已知的。突出强调了这些患者为当前理解常见代谢综合征的分子发病机制提供的经验教训。
