Research progress on the relationship between autophagy and chronic complications of diabetes

Abstract

Diabetes is a common metabolic disease whose hyperglycemic state can induce diverse complications and even threaten human health and life security. Currently, the treatment of diabetes is restricted to drugs that regulate blood glucose and have certain accompanying side effects. Autophagy, a research hotspot, has been proven to be involved in the occurrence and progression of the chronic complications of diabetes. Autophagy, as an essential organismal defense mechanism, refers to the wrapping of cytoplasmic proteins, broken organelles or pathogens by vesicles, which are then degraded by lysosomes to maintain the stability of the intracellular environment. Here, we review the relevant aspects of autophagy and the molecular mechanisms of autophagy in diabetic chronic complications, and further analyze the impact of improving autophagy on diabetic chronic complications, which will contribute to a new direction for further prevention and treatment of diabetic chronic complications.

Keywords: autophagy; chronic complications; diabetes drug; molecular mechanism; regulation.

FIGURE 1

General process of autophagy. Autophagy is a process that engulfs its own cytoplasmic proteins or organelles and encapsulates them into vesicles and fuses with lysosomes to form autolysosomes that degrade their encapsulated contents, realizing the cell’s own metabolic needs and the renewal of certain organelles.

FIGURE 2

Diabetes complications. The high-glucose state of diabetes can contribute to diverse complications such as diabetic microangiopathy and peripheral neuropathy. Some of these diabetic microangiopathies involve retinopathy, nephropathy and heart disease, such as Retinopathy, Blind, Nephropathy, Proteinuria, Podocytes, Vascular and Cardiomyopathy. In contrast, peripheral neuropathy presents with Amputation and Schwann cells.

FIGURE 3

Molecular mechanisms of autophagy associated with chronic complications of diabetes. mTORC1 regulates the initiation of autophagy by inhibiting the phosphorylation of the ULK1 complex and has a bidirectional effect on pancreatic β-cells. AMPK can impact autophagy by activating phosphorylation of ULK1 or regulating the PI3K complex. Autophagy and ROS can be mediated by each other. ROS activates autophagy by increasing beclin-1 expression and over-suppressing mTORC1, while autophagy can maintain ROS levels by clearing mitochondria. ER is an essential site of protein folding, while ER stress-mediated autophagy is associated with IRE1α, PERK, ATF6 and Ca²⁺ signaling pathways.