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

Table 1

The roles of mTOR (mTORC1) in diabetic nephropathy.

Experimental type	Renal outcome/phenotype	Mechanism	Reference
S6 Kinase 1^−/− mice	Renal hypertrophy↓	Inhibition of p70S6 kinase	Chen et al. [18]
Rapamycin (db/db mice)	Renal and glomerular hypertrophy↓	eEF2 kinase phosphorylation and laminin 𝛽1 expression	Sataranatarajan et al. [19]
Rapamycin (STZ-diabetic mice)	Renal hypertrophy↓	Inhibition of p70S6 kinase	Sakaguchi et al. [20]
Sirolimus (STZ-diabetic rats)	Glomerular hypertrophy↓, podocyte loss↓	Decreases of TGF-𝛽 and VEGF expression	Wittmann et al. [21]
Rapamycin (db/db mice)	Albuminuria↓, glomerular lesion↓	Inhibition of p70S6 kinase	Mori et al. [22]
Rapamycin (STZ-diabetic rats)	Albuminuria↓, glomerular lesion↓, and inflammation↓	Decreases of TGF-𝛽, VEGF, and MCP-1 expression	Yang et al. [23]
Rapamycin (STZ-diabetic rats)	Albuminuria↓, glomerular lesion↓	Decreases of TGF-𝛽, CTGF, and 𝛼-SMA expression	Lloberas et al. [24]
Gas6^−/− mice	Glomerular hypertrophy↓, mesangial expansion↓	Inhibition of akt and p70S6 kinase	Nagai et al. [25]
Rapamycin (HFD-induced obesity)	Proximal tubular cell damage↓	Increase of autophagy activity	Yamahara et al. [26]
Podocyte-specific raptor-heterozygous mice (db/db mice)	Albuminuria↓, glomerular lesion↓	Inhibition of mislocalization of nephrin	Inoki et al. [27]
Podocyte-specific raptor-heterozygous mice (STZ-diabetic mice)	Albuminuria↓, glomerular lesion↓	Inhibition of podocyte loss	Godel et al. [28]

STZ; streptozotocin, PTECs: proximal tubular epithelial cells, TGF𝛽: transforming growth factor 𝛽, VEGF: vascular endothelial growth factor, MCP-1: monocyte chemoattractant protein-1, CTGF: connective tissue growth factor, 𝛼-SMA: 𝛼-smooth muscle actin, and PARP: p(ADP-ribose) polymerases.