Autophagy as a Therapeutic Target in Diabetic Nephropathy

Figure 4

Regulation of autophagy by nutrient and intracellular stresses and the relationship between autophagy and the progression of diabetic nephropathy. Under normal conditions, intracellular stresses such as hypoxia, mitochondrial ROS, and ER stress induce autophagy. Nutrient depletion enhances autophagy by inhibiting mTORC1 and by activating AMPK and Sirt1. This activation of autophagy helps to maintain intracellular homeostasis and may have renoprotective effects. In contrast, under diabetic conditions, high glucose or FFA levels increase intracellular stresses, leading to the progression of diabetic nephropathy. Furthermore, nutrient excess and high glucose levels under diabetic conditions inhibit autophagy by inhibiting AMPK and Sirt1, and by activating mTORC1. This inactivation of autophagy may reinforce the progression of diabetic nephropathy. ROS: reactive oxygen species; ER: endoplasmic reticulum; mTORC1: mammalian target of rapamycin (mTOR) complex 1 (mTORC1); AMPK: AMP-activated protein kinase; FFA: free fatty acid.