Dupont Joëlle, Scaramuzzi Rex J
UMR 7247 Physiologie de la Reproduction et des Comportements, CNRS, INRA, Université de Tours, Institut Français du Cheval et de l'Équitation, 37380 Nouzilly, France.
UMR 7247 Physiologie de la Reproduction et des Comportements, CNRS, INRA, Université de Tours, Institut Français du Cheval et de l'Équitation, 37380 Nouzilly, France Department of Comparative Biological Sciences, Royal Veterinary College, Hawkshead Lane, South Mimms, Hertfordshire AL9 7TA, U.K.
Biochem J. 2016 Jun 1;473(11):1483-501. doi: 10.1042/BCJ20160124.
Data derived principally from peripheral tissues (fat, muscle and liver) show that insulin signals via diverse interconnecting intracellular pathways and that some of the major intersecting points (known as critical nodes) are the IRSs (insulin receptor substrates), PI3K (phosphoinositide kinase)/Akt and MAPK (mitogen-activated protein kinase). Most of these insulin pathways are probably also active in the ovary and their ability to interact with each other and also with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) signalling pathways enables insulin to exert direct modulating influences on ovarian function. The present paper reviews the intracellular actions of insulin and the uptake of glucose by ovarian tissues (granulosa, theca and oocyte) during the oestrous/menstrual cycle of some rodent, primate and ruminant species. Insulin signals through diverse pathways and these are discussed with specific reference to follicular cell types (granulosa, theca and oocyte). The signalling pathways for FSH in granulosa cells and LH in granulosa and theca cells are summarized. The roles of glucose and of insulin-mediated uptake of glucose in folliculogenesis are discussed. It is suggested that glucose in addition to its well-established role of providing energy for cellular function may also have insulin-mediated signalling functions in ovarian cells, involving AMPK (AMP-dependent protein kinase) and/or hexosamine. Potential interactions of insulin signalling with FSH or LH signalling at critical nodes are identified and the available evidence for such interactions in ovarian cells is discussed. Finally the action of the insulin-sensitizing drugs metformin and the thiazolidinedione rosiglitazone on follicular cells is reviewed.
主要来自外周组织（脂肪、肌肉和肝脏）的数据表明，胰岛素通过多种相互连接的细胞内途径发出信号，一些主要的交叉点（称为关键节点）是胰岛素受体底物（IRSs）、磷酸肌醇激酶（PI3K）/蛋白激酶B（Akt）和丝裂原活化蛋白激酶（MAPK）。这些胰岛素途径中的大多数可能在卵巢中也有活性，它们相互作用以及与促卵泡激素（FSH）和促黄体生成素（LH）信号通路相互作用的能力，使胰岛素能够对卵巢功能施加直接的调节影响。本文综述了胰岛素在一些啮齿动物、灵长类动物和反刍动物发情期/月经周期中对卵巢组织（颗粒细胞、卵泡膜细胞和卵母细胞）的细胞内作用以及葡萄糖的摄取情况。胰岛素通过多种途径发出信号，并结合卵泡细胞类型（颗粒细胞、卵泡膜细胞和卵母细胞）进行了具体讨论。总结了颗粒细胞中FSH以及颗粒细胞和卵泡膜细胞中LH的信号通路。讨论了葡萄糖以及胰岛素介导的葡萄糖摄取在卵泡发生中的作用。有人提出，葡萄糖除了具有为细胞功能提供能量这一已确定的作用外，在卵巢细胞中可能还具有胰岛素介导的信号功能，涉及AMP依赖的蛋白激酶（AMPK）和/或己糖胺。确定了胰岛素信号在关键节点与FSH或LH信号的潜在相互作用，并讨论了卵巢细胞中此类相互作用的现有证据。最后综述了胰岛素增敏药物二甲双胍和噻唑烷二酮类药物罗格列酮对卵泡细胞的作用。
