mTORC1 signaling and diabetic kidney disease.

IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM Diabetology International Pub Date : 2024-06-20 eCollection Date: 2024-10-01 DOI:10.1007/s13340-024-00738-1
Vinamra Swaroop, Eden Ozkan, Lydia Herrmann, Aaron Thurman, Olivia Kopasz-Gemmen, Abhiram Kunamneni, Ken Inoki
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Abstract

Diabetic kidney disease (DKD) represents the most lethal complication in both type 1 and type 2 diabetes. The disease progresses without obvious symptoms and is often refractory when apparent symptoms have emerged. Although the molecular mechanisms underlying the onset/progression of DKD have been extensively studied, only a few effective therapies are currently available. Pathogenesis of DKD involves multifaced events caused by diabetes, which include alterations of metabolisms, signals, and hemodynamics. While the considerable efficacy of sodium/glucose cotransporter-2 (SGLT2) inhibitors or angiotensin II receptor blockers (ARBs) for DKD has been recognized, the ever-increasing number of patients with diabetes and DKD warrants additional practical therapeutic approaches that prevent DKD from diabetes. One plausible but promising target is the mechanistic target of the rapamycin complex 1 (mTORC1) signaling pathway, which senses cellular nutrients to control various anabolic and catabolic processes. This review introduces the current understanding of the mTOR signaling pathway and its roles in the development of DKD and other chronic kidney diseases (CKDs), and discusses potential therapeutic approaches targeting this pathway for the future treatment of DKD.

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mTORC1 信号传导与糖尿病肾病。
糖尿病肾病(DKD)是 1 型和 2 型糖尿病最致命的并发症。这种疾病在没有明显症状的情况下发展,而且在出现明显症状时往往是难治性的。尽管对 DKD 发病/进展的分子机制进行了广泛研究,但目前只有少数几种有效疗法。DKD 的发病机制涉及糖尿病引起的多方面事件,包括代谢、信号和血液动力学的改变。虽然钠/葡萄糖共转运体-2(SGLT2)抑制剂或血管紧张素 II 受体阻滞剂(ARB)对 DKD 的疗效已得到认可,但糖尿病和 DKD 患者人数的不断增加需要更多实用的治疗方法,以防止 DKD 从糖尿病发展为 DKD。雷帕霉素复合体 1(mTORC1)信号通路是一个看似合理但很有前景的靶点,它能感知细胞营养物质,控制各种合成代谢和分解代谢过程。这篇综述介绍了目前对mTOR信号通路的理解及其在DKD和其他慢性肾脏疾病(CKD)发展过程中的作用,并讨论了针对这一通路的潜在治疗方法,以便在未来治疗DKD。
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来源期刊
Diabetology International
Diabetology International ENDOCRINOLOGY & METABOLISM-
CiteScore
3.90
自引率
4.50%
发文量
42
期刊介绍: Diabetology International, the official journal of the Japan Diabetes Society, publishes original research articles about experimental research and clinical studies in diabetes and related areas. The journal also presents editorials, reviews, commentaries, reports of expert committees, and case reports on any aspect of diabetes. Diabetology International welcomes submissions from researchers, clinicians, and health professionals throughout the world who are interested in research, treatment, and care of patients with diabetes. All manuscripts are peer-reviewed to assure that high-quality information in the field of diabetes is made available to readers. Manuscripts are reviewed with due respect for the author''s confidentiality. At the same time, reviewers also have rights to confidentiality, which are respected by the editors. The journal follows a single-blind review procedure, where the reviewers are aware of the names and affiliations of the authors, but the reviewer reports provided to authors are anonymous. Single-blind peer review is the traditional model of peer review that many reviewers are comfortable with, and it facilitates a dispassionate critique of a manuscript.
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