Table 1.

Protective effects of insulin signaling activators or insulin-signaling targeted therapies against various diseases.

Categories	Drug	Doses	Experimental Model (Human/Animal)	Disease Model	Mode of Action	References
Natural products	Resveratrol	20 µM	Human, mouse	Kidney mesangial cells	Induced AdipoR1 mRNA and protein levels Improved FOXO1 activity	Ji et al. [160]
	Gallic acid	20–40 mg	Rat	Type I diabetic nephropathy	Decreased TGF-β1 levels and creatinine clearance	Garud, and Kulkarni, [162]
	Mangiferin	40 mg	Human	Type 2 diabetes	Reduced blood glucose levels, AST, ALT, and ALP Activated β-catenin	Du et al. [163]
	Saxagliptin	2.5–5 mg	Human, mouse	Type 2 diabetes	Decreased glucagon production Increased insulin production Inhibited DPP-4 activation	Rasouli et al. [168]
	Alpha-glucosidase inhibitors	25 mg		Type 2 diabetes	Reduced renal function Produced hypoglycemic effect	Kumar et al. [169]; Usman et al. [158]
Secondary alcohol	3β-Taraxerol	200 mg	Human	Type 2 diabetes	Improved pancreatic function Increased insulin secretion	Rasouli et al. [161]
Organic compounds	Sulfonylureas	5 mg	Human	Type 2 diabetes	Increased insulin secretion	Nathan et al. [155]
FDA/Commercial Drugs	Metformin	5 mg	Human, mouse, rat	Type 2 diabetes	Improved glucose uptake, lipotoxicity, and antioxidant activities	Pan et al. [153]
	Miglitol	25 mg	Human	Type 2 diabetes	Inhibited α-glucosidase Induced antihyperglycemic activities	Rasouli et al. [168]
	SGLT2 inhibitors	5–10 mg	Human	Type 2 diabetes	Decreased glucose absorption Increased anti-inflammatory and antioxidative activities	Whalen et al. [156]
	Thiazolidinediones	8 mg	Human	Type 2 diabetes	Acted as PPARγ agonist	Soccio et al. [157]
	Colesevelam	3.75 g	Human	Type 2 diabetes	Increased triglycerides Decreased LDLc	Feingold, [170]
	Gallotannins	10–100 ng/mL	Human, rat	Type 2 diabetes	Increased PI3K mRNA and GLUT4 expressions	Kanaujia et al. [165]
	DPP-IV inhibitors	50 mg	Human	Type 2 diabetes	Stimulated incretin system and SGLT-2	Jose and Inzucchi, [166]
	Oxovanadium complex	200 mg	Mouse	Diabetic mice	Increased blood SOD, GSH, TP, and LC3 levels	El-Shafey and Elsherbiny, [167]
	Acarbose	50 mg	human	Type 2 diabetes	Inhibited α-glucosidase and α-amylase	Rasouli et al. [168]