Abstract：
Insulin is a hormone that positively regulates anabolism and cell growth, whereas diabetes mellitus is a disease characterized by hyperglycemia associated with impaired insulin action. My colleagues and I have elucidated multifaceted insulin action in various tissues mainly by means of model mice. In the liver, insulin regulates endoplasmic reticulum (ER) stress response during feeding, whereas ER stress \'response failure\' contributes to the development of steatohepatitis comorbid with diabetes. Not only the liver but also the proximal tubules of the kidney are important in the regulation of gluconeogenesis, and we revealed that insulin suppresses gluconeogenesis in accordance with absorbed glucose in the latter tissue. In skeletal muscle, another important insulin-targeted tissue, impaired insulin/IGF-1 signaling leads not only to sarcopenia, an aging-related disease of skeletal muscle, but also to osteopenia and shorter longevity. Aging is regulated by adipokines as well, and it should be considered that aging could be accelerated by \'imbalanced adipokines\' in patients with a genetic background of progeria. Moreover, we reported the effects of intensive multifactorial intervention on diabetic vascular complications and mortality in patients with type 2 diabetes in a large-scale clinical trial, the J-DOIT3, and the results of subsequent sub-analyses of renal events and fracture events. Various approaches of research enable us of endocrinologists to elucidate the physiology of hormone signaling, the mechanisms underlying the development of endocrine diseases, and the appropriate treatment measures. These approaches also raise fundamental questions, but addressing them in an appropriate manner will surely contribute to the further development of endocrinology.
摘要：
胰岛素是一种积极调节合成代谢和细胞生长的激素，而糖尿病是一种以胰岛素作用受损的高血糖为特征的疾病。我和我的同事主要通过模型小鼠阐明了胰岛素在各种组织中的多方面作用。在肝脏中，胰岛素调节喂养过程中的内质网（ER）应激反应，而内质网应激“反应失败”有助于脂肪性肝炎合并糖尿病的发展。不仅肝脏，而且肾脏的近端小管在糖异生的调节中也很重要，我们发现胰岛素与后者组织中吸收的葡萄糖一致抑制糖异生。在骨骼肌中，另一个重要的胰岛素靶向组织，胰岛素/IGF-1信号传导受损不仅导致肌肉减少症，一种与衰老相关的骨骼肌疾病，而且骨质减少和寿命较短。衰老也受脂肪因子调节，应该考虑到，在有早衰症遗传背景的患者中，“脂肪因子失衡”可能会加速衰老。此外，我们在一项大规模临床试验中报道了强化多因素干预对2型糖尿病患者糖尿病血管并发症和死亡率的影响,J-DOIT3,以及随后对肾脏事件和骨折事件的亚分析结果.各种研究方法使我们内分泌学家能够阐明激素信号的生理学，内分泌疾病发展的潜在机制，以及相应的治疗措施。这些方法也提出了基本问题，但是以适当的方式解决这些问题肯定会有助于内分泌学的进一步发展。
