The Role of Organelle Stresses in Diabetes Mellitus and Obesity: Implication for Treatment

Table 3

Treatment targeting organelle stress for diabetes mellitus and obesity.

Agent	Specific mechanism	Highest level of studies	Result
Tauroursodeoxycholic acid	Chemical chaperone	Randomized controlled trials	Improved insulin sensitivity in muscle and liver in obese individuals [86]
Phenylbutyrate	Chemical chaperone	Randomized controlled trials	Improved insulin sensitivity and beta-cell function in lipid-infused individuals [87]
Azoramide	ATF6 activators	Rodents	Improves insulin sensitivity and beta-cell function in obese mice [89]
Valproate	Increasing GRPP78	Rodents	Ameliorates atherosclerosis and hepatic steatosis in Apoe^−/−mice [90]
L-Carnitine or carnitine-orotate	Fatty acid transfer for beta-oxidation	Randomized controlled trials	Twelve of 17 studies showing improved insulin sensitivity or glycemic control in type 2 diabetic patients or alleviation of hepatic steatosis [98, 99]
Co-enzyme Q10	Electron carrier from complex I and II to complex III	Randomized controlled trials	No net effect on glycemic control in type 2 diabetic patients [100]
α-lipoic acid	Antioxidant	Randomized controlled trials; rodent	Weight-reducing, glucose-lowering, and insulin-sensitizing effect; prevention of hepatic steatosis [101–110]
Vitamin E	Antioxidant	Randomized controlled trials	Inconsistent results on glycemic control [111–115]; reduced hepatic steatosis [122]
N-acetylcysteine	Antioxidant	Rodents	Prevents diet-induced obesity [116–118]
Peptide SS31	Mitochondria-targeted antioxidant peptide	Rodent	Improved glucose tolerance in diet-induced obese mice [38]
Resveratrol	SIRT1 agonist	Randomized controlled trials	Improved insulin sensitivity and glycemic control in diabetic patients; no effect in nondiabetic patients [120];
GSK5182	Estrogen-related receptor gamma inverse agonist	Rodents	Reduces hyperglycemia due to inhibition of hepatic gluconeogenesis [121]
Trehalose, imanitib	Enhance autophagy	Rodents	Improved glucose tolerance and insulin sensitivity in obese mice [84]
Dh404	Nrf2 activator	Rodents	Increased viability of islet by enhancing autophagy [123]