Department of Endocrinology, University of Pisa, Via Paradisa 2, 50124, Pisa, Italy.
J Mammary Gland Biol Neoplasia. 2013 Dec;18(3-4):277-89. doi: 10.1007/s10911-013-9303-7. Epub 2013 Oct 24.
Obesity and the Metabolic Syndrome are associated with multiple factors that may cause an increased risk for cancer and cancer-related mortality. Factors involved include hyperinsulinemia, hyperglycemia, hyperlipidemia and IGFs. Insulin resistance is also associated with alterations in the levels of proinflammatory cytokines, chemokines, adipokines (leptin, adiponectin) that may also be contributing factors. The insulin family of proteins is ubiquitously expressed and has pleiotropic effects on metabolism and growth. However insulin, IGF-1 and particularly IGF-2 have been identified as tumor promoters in multiple studies. Mouse models have focused on insulin and IGF-1 and their receptors as being involved in tumor progression and metastases. The role of the insulin receptor as either mediating the effects on tumors or as compensating for the insulin-like growth factor receptor has arisen. Its role has been supported by preclinical studies and the importance of insulin resistance and hyperinsulinemia in obesity and early diabetes. Since the focus of this review is the insulin-family we will focus on insulin, IGF-1 and IGF-2.
肥胖和代谢综合征与多种因素相关，这些因素可能会增加癌症风险和癌症相关死亡率。涉及的因素包括高胰岛素血症、高血糖、高血脂和 IGFs。胰岛素抵抗也与促炎细胞因子、趋化因子和脂肪因子（瘦素、脂联素）水平的改变有关，这些改变也可能是促成因素。胰岛素家族蛋白广泛表达，对代谢和生长具有多种效应。然而，多项研究已经确定胰岛素、IGF-1 尤其是 IGF-2 是肿瘤促进剂。小鼠模型主要关注胰岛素和 IGF-1 及其受体在肿瘤进展和转移中的作用。胰岛素受体作为介导肿瘤作用的介质或作为补偿胰岛素样生长因子受体的作用已经出现。临床前研究支持其作用，并且肥胖和早期糖尿病中胰岛素抵抗和高胰岛素血症的重要性也得到了证实。由于本综述的重点是胰岛素家族，我们将重点关注胰岛素、IGF-1 和 IGF-2。
