Carpentier André C
Department of Medicine, Division of Endocrinology, University of Sherbrooke, Québec, J1H 5N4, Canada.
Diabetes Metab. 2008 Apr;34(2):97-107. doi: 10.1016/j.diabet.2007.10.009. Epub 2008 Mar 18.
Insulin resistance (IR) and impaired glucose-stimulated insulin secretion (GSIS) are the two primary pathophysiological abnormalities leading to the development of type 2 diabetes (T2D). Over the past two decades, a large body of work has implicated enhanced delivery of fatty acids to non-adipose tissues in the development of both IR and impaired GSIS. As the net whole-body import of fatty acids occurs in the postprandial state, tissue fatty acid overexposure has been linked to this physiological state. Although many advances have been made in our understanding of these lipotoxic effects at the cellular level, the precise mechanisms of lipotoxicity at the whole-body level in humans during the development of T2D is still a subject of debate. Important advances continue to be made in our understanding of the mechanisms that regulate postprandial fatty acid delivery to tissues and their metabolism. This review focuses on those mechanisms and on the potential implication of their dysregulation for tissue lipotoxicity in the development of T2D.
胰岛素抵抗（IR）和葡萄糖刺激的胰岛素分泌受损（GSIS）是导致2型糖尿病（T2D）发生的两个主要病理生理异常。在过去二十年中，大量研究表明，脂肪酸向非脂肪组织的输送增加与IR和GSIS受损的发生有关。由于餐后状态下会发生全身脂肪酸的净摄取，组织脂肪酸过度暴露与这种生理状态相关。尽管我们在细胞水平上对这些脂毒性作用的理解取得了许多进展，但在T2D发生过程中人体全身水平的脂毒性确切机制仍存在争议。我们对调节餐后脂肪酸向组织输送及其代谢的机制的理解不断取得重要进展。本综述重点关注这些机制及其失调对T2D发生过程中组织脂毒性的潜在影响。
