Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada.
Department of Pathology, University of Oklahoma Health Sciences Center, Stephenson Cancer Center, Harold Hamm Diabetes Center, Oklahoma City, OK, USA.
Diabetes Metab J. 2021 May;45(3):285-311. doi: 10.4093/dmj.2020.0250. Epub 2021 Mar 29.
The relative insufficiency of insulin secretion and/or insulin action causes diabetes. However, obesity and type 2 diabetes mellitus can be associated with an absolute increase in circulating insulin, a state known as hyperinsulinemia. Studies are beginning to elucidate the cause-effect relationships between hyperinsulinemia and numerous consequences of metabolic dysfunctions. Here, we review recent evidence demonstrating that hyperinsulinemia may play a role in inflammation, aging and development of cancers. In this review, we will focus on the consequences and mechanisms of excess insulin production and action, placing recent findings that have challenged dogma in the context of the existing body of literature. Where relevant, we elaborate on the role of specific signal transduction components in the actions of insulin and consequences of chronic hyperinsulinemia. By discussing the involvement of hyperinsulinemia in various metabolic and other chronic diseases, we may identify more effective therapeutics or lifestyle interventions for preventing or treating obesity, diabetes and cancer. We also seek to identify pertinent questions that are ripe for future investigation.
胰岛素分泌和/或作用相对不足会导致糖尿病。然而，肥胖和 2 型糖尿病可能与循环胰岛素绝对增加有关，这种状态被称为高胰岛素血症。研究开始阐明高胰岛素血症与代谢功能障碍的许多后果之间的因果关系。在这里，我们回顾了最近的证据，表明高胰岛素血症可能在炎症、衰老和癌症发展中发挥作用。在这篇综述中，我们将重点讨论胰岛素过量产生和作用的后果和机制，同时将最近的发现置于现有文献的背景下，这些发现对传统观点提出了挑战。在相关情况下，我们详细阐述了特定信号转导成分在胰岛素作用和慢性高胰岛素血症后果中的作用。通过讨论高胰岛素血症在各种代谢和其他慢性疾病中的作用，我们可以确定更有效的治疗方法或生活方式干预措施，以预防或治疗肥胖、糖尿病和癌症。我们还试图确定未来研究中亟待解决的问题。
