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] |