Crosstalk between autophagy and insulin resistance: evidence from different tissues

Table 1 FDA-approved medicines with established indications on metabolism that could modulate autophagy

Medicine	Target	Mechanism of action	Tissue	References
Rapamycin	↓ mTOR signaling	- Inhibits mTOR	Adipose and liver	[137, 304]
Imatinib	- Inhibits BCR-ABL/PDGFR/KIT - Increases ROS	- Lowers mitochondrial membrane potential - Inhibits oxygen consumption and glycolysis - Promotes WAT browning - Disrupts the PI3K/Akt/FOXO4/ATF5/mTOR pathway	–	[296, 297]
Pioglitazone	Activates the PPAR and NAF-1	- Decrease apoptosis and inflammation	Adipose and liver	[298]
Liraglutide	↓ mTOR signaling	- Improves hepatic lipase activity - Decreases hepatic lipid content - Reduces glucose levels	Liver	[300]
Metformin	↑ AMPK	- Restoring SIRT1-mediated autophagy induction	Liver	[284, 293]
Resveratrol	↓ AKT1–mTOR pathway ↑ AMPK	- Activates sirtuin - Inhibits ribosomal protein S6 kinase	Adipose and liver	[305, 306]
Trehalose	Attenuates the phosphorylated levels of Foxo1 and p38 MAPK	- Blocks glucose transport	Muscle and liver	[294, 295]
Bortezomib	↑ AMPK	- Reduces the activation of the mTOR pathway, ER stress, and inflammation	Adipocytes	[299]
Sitagliptin	↑ AMPK	- Decrease TG, LDL-c, and oxidative stress - Suppress the mTOR signaling pathway	–	[118, 302]
Ezetimibe	- Inhibits cholesterol absorption	- Inhibits steatohepatitis via AMPK–TFEB- mediated activation of autophagy - Inhibits NLRP3 inflammasome	Liver	[307]

AMPK AMP-activated protein kinase, ATF5 activating transcription factor 5, ER endoplasmic reticulum, FOXO1 Forkhead Box O1, LDL low-density lipoprotein, mTOR mammalian target of rapamycin, NAF-1 nutrient-deprivation autophagy factor-1, PDGFR platelet-derived growth factor receptor, PI3K phosphoinositide 3-kinase, PPAR peroxisome proliferator-activated receptors, TG triacylglycerol, WAT white adipose tissue. ↑ indicates "increase" and ↓ indicates "decrease"

ISSN: 2047-783X