Role of Nutrient-Sensing Signals in the Pathogenesis of Diabetic Nephropathy

Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. The multipronged drug approach still fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to improve the prognosis of diabetic nephropathy is urgently required. Nu...

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Bibliographic Details
Published in:BioMed research international 2014-01, Vol.2014 (2014), p.1-9
Main Authors: Kume, Shinji, Koya, Daisuke, Uzu, Takashi, Maegawa, Hiroshi
Format: Article
Language:English
Subjects:
Animals
Autophagy - genetics
Development and progression
Diabetic nephropathies
Diabetic Nephropathies - diagnosis
Diabetic Nephropathies - metabolism
Diabetic Nephropathies - physiopathology
Food
Glucose
Humans
Kinases
Mechanistic Target of Rapamycin Complex 1
Metabolic Networks and Pathways - genetics
Multiprotein Complexes - metabolism
Nephrology
Podocytes - metabolism
Podocytes - pathology
Protein Kinases - metabolism
Review
Rodents
Sirtuin 1 - metabolism
Studies
TOR Serine-Threonine Kinases - metabolism
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Summary:Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. The multipronged drug approach still fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to improve the prognosis of diabetic nephropathy is urgently required. Nutrient-sensing signals and their related intracellular machinery have evolved to combat prolonged periods of starvation in mammals; and these systems are conserved in the kidney. Recent studies have suggested that the activity of three nutrient-sensing signals, mTORC1, AMPK, and Sirt1, is altered in the diabetic kidney. Furthermore, autophagy activity, which is regulated by the above-mentioned nutrient-sensing signals, is also altered in both podocytes and proximal tubular cells under diabetic conditions. Under diabetic conditions, an altered nutritional state owing to nutrient excess may disturb cellular homeostasis regulated by nutrient-responsible systems, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing relationships between nutrient-sensing signals, autophagy, and diabetic nephropathy and suggest the therapeutic potential of nutrient-sensing signals in diabetic nephropathy.
ISSN:2314-6133
2314-6141
DOI:10.1155/2014/315494