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.

Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation

“…The anti-apoptotic effects of metformin in a rat model of DR were characterised by decreases in the serum levels of oxidative stress markers and caspase-3 expression [ 134 ]. AMPK-mTOR signalling can trigger autophagy in RPE cells and thus can play a crucial role in the maintenance and self-clearance of normal cellular function [ 135 ]. Metformin as an agonist of the AMPK pathway may reduce RPE cell and photoreceptor cell death in the prevention and treatment of DR [ 135 ].…”

“…AMPK-mTOR signalling can trigger autophagy in RPE cells and thus can play a crucial role in the maintenance and self-clearance of normal cellular function [ 135 ]. Metformin as an agonist of the AMPK pathway may reduce RPE cell and photoreceptor cell death in the prevention and treatment of DR [ 135 ]. In this regard, the protective effect of metformin on endothelial cells under HG conditions could be partly explained by its role in attenuating autophagy via GLI1-dependent HG signalling activation.…”

SGLT2 inhibitors and autophagy in diabetes

“…35,36 Autophagy is essential for both energy homeostasis and metabolic balance by degrading macromolecules into micromolecules and recycling and synthesis of other substances. 11 Autophagy catabolizes metabolic lipids to short-chain free fatty acids to provide substrate for mitochondrial energy production. 11 Autophagy has important roles in the process of organelle renewal by degrading damaged organelles and proteins to facilitate new organelle synthesis.…”

“…11 According to how substances are transported to the lysosome, autophagy has three forms in mammals, microautophagy, macroautophagy and chaperone-mediated autophagy that all happen within the lysosome. 11 They are activated by complex cellular machinery including growth factors, catabolic enzymes and signaling molecules. 9 F I G U R E 1 SGLT2 inhibitors induce glycosuria (as well as natriuresis) by inhibition of SGLT2 proteins in tubular cells of renal proximal tubules resulting in a reduction of blood glucose (Created with BioRender.com).…”

“…40 Thus, it is essential for glucose homeostasis and metabolic processes. 41 However, it may be a pathologic process in diabetes and may induce tissue injury 9,11 ; therefore, autophagy may be a therapeutic target for the prevention of diabetic complications. 42 Since autophagy contributes to the maintenance of intracellular homeostasis in most biological cells, its altered form is associated with instability of these cells and aberrant apoptosis especially in diabetes.…”