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Updated: Jun 9, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
mTORC1 signaling and diabetic kidney disease
Vinamra Swaroop1, Eden Ozkan1, Lydia Herrmann1
1Life Sciences Institute, University of Michigan, Ann Arbor, USA.
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.
Insights
Diabetic kidney disease (DKD) is a severe diabetes complication. Targeting the mTORC1 pathway offers a promising new therapeutic strategy for preventing and treating DKD.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Diabetic kidney disease (DKD) is a leading cause of mortality in diabetes patients.
- DKD often progresses asymptomatically and is difficult to treat once symptoms appear.
- Current therapies like SGLT2 inhibitors and ARBs have limitations, necessitating new approaches.
Purpose of the Study:
- To review the role of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway in DKD pathogenesis.
- To explore mTORC1 as a potential therapeutic target for DKD and other chronic kidney diseases (CKDs).
Main Methods:
- Literature review of studies on mTORC1 signaling in diabetes and kidney disease.
- Analysis of molecular mechanisms linking metabolic and hemodynamic changes to DKD.
- Discussion of existing and potential therapeutic strategies targeting mTORC1.
Main Results:
- The mTORC1 pathway is implicated in DKD development through nutrient sensing and regulation of cellular processes.
- Dysregulation of mTORC1 contributes to metabolic and signaling alterations in DKD.
- Targeting mTORC1 may offer a novel therapeutic avenue for DKD.
Conclusions:
- The mTORC1 pathway is a critical regulator in DKD pathogenesis.
- Inhibiting or modulating mTORC1 signaling presents a promising strategy for future DKD therapies.
- Further research into mTORC1-targeted treatments is warranted for diabetic and chronic kidney diseases.
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