The insulin receptor (IR) gene undergoes differential splicing that generates two IR isoforms, IR-A and IR-B. The physiological roles of IR isoforms are incompletely understood and appear to be determined by their different binding affinities for insulin-like growth factors (IGFs), particularly for IGF-2. Predominant roles of IR-A in prenatal growth and development and of IR-B in metabolic regulation are well established. However, emerging evidence indicates that the differential expression of IR isoforms may also help explain the diversification of insulin and IGF signaling and actions in various organs and tissues by involving not only different ligand-binding affinities but also different membrane partitioning and trafficking and possibly different abilities to interact with a variety of molecular partners. Of note, dysregulation of the IR-A/IR-B ratio is associated with insulin resistance, aging, and increased proliferative activity of normal and neoplastic tissues and appears to sustain detrimental effects. This review discusses novel information that has generated remarkable progress in our understanding of the physiology of IR isoforms and their role in disease. We also focus on novel IR ligands and modulators that should now be considered as an important strategy for better and safer treatment of diabetes and cancer and possibly other IR-related diseases.

中文翻译：

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生理和疾病中的胰岛素受体同工型：更新的观点。

胰岛素受体（IR）基因经过差异剪接，产生两种IR亚型，即IR-A和IR-B。对IR同工型的生理作用尚未完全理解，似乎是由它们对胰岛素样生长因子（IGFs），特别是对IGF-2的不同结合亲和力决定的。众所周知，IR-A在产前生长发育中的主要作用以及IR-B在代谢调节中的主要作用。然而，新出现的证据表明，IR同工型的差异表达还可能通过不仅涉及不同的配体结合亲和力，而且还涉及不同的膜分区和运输以及可能的不同能力，帮助解释了胰岛素和IGF信号在各种器官和组织中的多样化作用。与各种分子伴侣互动。值得注意的是 IR-A / IR-B比例的失调与胰岛素抵抗，衰老以及正常和赘生性组织的增殖活性增加有关，并且似乎维持有害作用。这篇综述讨论了新颖的信息，这些信息在我们对IR异构体的生理学及其在疾病中的作用的理解中产生了显着的进步。我们还将重点放在新型的IR配体和调节剂上，这些新的IR配体和调节剂现在应被视为更好，更安全地治疗糖尿病和癌症以及其他可能与IR相关的疾病的重要策略。这篇综述讨论了新颖的信息，这些信息在我们对IR同工型的生理学及其在疾病中的作用的理解中产生了显着进步。我们还将重点放在新型的IR配体和调节剂上，这些新的IR配体和调节剂现在应被视为更好，更安全地治疗糖尿病和癌症以及其他可能与IR相关的疾病的重要策略。这篇综述讨论了新颖的信息，这些信息在我们对IR同工型的生理学及其在疾病中的作用的理解中产生了显着进步。我们还将重点放在新型的IR配体和调节剂上，这些新的IR配体和调节剂现在应被视为更好，更安全地治疗糖尿病和癌症以及其他可能与IR相关的疾病的重要策略。