Pathophysiological roles of nutrient-sensing mechanisms in diabetes and its complications

  • Shinji KumeEmail author
Review Article


Diabetic nephropathy, which is characterized by increased albuminuria, has been the most common cause of end-stage kidney disease for many years in Japan and many other countries. Although the renal prognosis of the disease has been improving in recent years because of the clinical implementation of strict glucose, blood pressure, and lipid controls, some diabetes patients continue to exhibit treatment-resistant macroalbuminuria leading to end-stage kidney disease. Furthermore, renal function decline without macroalbuminuria in diabetes is an emerging issue in Japan, which might be partly due to aging. Thus, a novel therapeutic strategy is needed to further improve renal outcome in diabetes patients. We have recently reported the involvement of dysregulation of intracellular nutrient-sensing signals and the related cellular process, autophagy, in the pathogenesis of diabetic nephropathy and abnormal insulin secretion pattern in type 2 diabetes. This review discusses potential roles of intracellular nutrient-sensing signals and autophagy as novel therapeutic targets for type 2 diabetes and diabetic nephropathy.


Type 2 diabetes Diabetic nephropathy Sirt1 AMPK mTORC1 Autophagy 



This review is a summary of my presentation in the Lilly Award Lecture at the 62nd annual meeting of the Japan Diabetes Society, Sendai, Japan. I would like to express sincere gratitude to Professor Hiroshi Maegawa, Professor Daisuke Koya, Professor Masakazu Haneda, Professor Atsunori Kashiwagi, Professor Ryuichi Kikkawa, and all members of department of medicine, Shiga University of Medical Science for their guidance and support.

Compliance with ethical standards

Conflict of interest

Shinji Kume declares that he has no conflict of interest.

Statement of animal and/or human participants

This article does not contain any studies with human or animal subjects.


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Copyright information

© The Japan Diabetes Society 2019

Authors and Affiliations

  1. 1.Department of MedicineShiga University of Medical ScienceOtsuJapan

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