Exploring mechanisms of insulin action and strategies to treat diabetes

IF 1.3 4区 医学 Q4 ENDOCRINOLOGY & METABOLISM Endocrine journal Pub Date : 2024-05-29 DOI:10.1507/endocrj.ej24-0003
Takayoshi Sasako
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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.

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探索胰岛素作用机制和糖尿病治疗策略
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导致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不同组织中的多方面作用。在肝脏中,胰岛素调节进食时的内质网(ER)应激反应,而ER应激 "反应失败 "则导致糖尿病合并脂肪性肝炎的发生。不仅肝脏,肾脏近端肾小管在调节葡萄糖生成方面也很重要,我们发现胰岛素会根据肾脏近端肾小管吸收葡萄糖的情况抑制葡萄糖生成。骨骼肌是另一个重要的胰岛素靶组织,胰岛素/IGF-1 信号受损不仅会导致与骨骼肌衰老相关的 "肌肉疏松症",还会导致骨质疏松和寿命缩短。衰老也受脂肪因子的调节,因此,在有早衰症遗传背景的患者中,"失衡的脂肪因子 "可能会加速衰老。此外,我们还报告了在大规模临床试验 J-DOIT3 中对 2 型糖尿病患者进行强化多因素干预对糖尿病血管并发症和死亡率的影响,以及随后对肾脏事件和骨折事件进行子分析的结果。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、内分泌疾病的发病机制以及适当的治疗措施。这些方法也提出了一些基本问题,但以适当的方式解决这些问题必将有助于内分泌学的进一步发展。
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来源期刊
Endocrine journal
Endocrine journal 医学-内分泌学与代谢
CiteScore
4.30
自引率
5.00%
发文量
224
审稿时长
1.5 months
期刊介绍: Endocrine Journal is an open access, peer-reviewed online journal with a long history. This journal publishes peer-reviewed research articles in multifaceted fields of basic, translational and clinical endocrinology. Endocrine Journal provides a chance to exchange your ideas, concepts and scientific observations in any area of recent endocrinology. Manuscripts may be submitted as Original Articles, Notes, Rapid Communications or Review Articles. We have a rapid reviewing and editorial decision system and pay a special attention to our quick, truly scientific and frequently-citable publication. Please go through the link for author guideline.
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