Table 2.
Metabolic and anti-inflammatory effects of modern antidiabetic preparations.
| Group of Preparation |
Mechanism of Action |
Metabolic Effects |
Anti-Inflammatory Effects |
|---|---|---|---|
| Sulfonylurea preparations | Bind to the sulfonylurea receptor (SUR) of ATP-sensitive potassium channel on pancreatic β cells | Enhance the release of insulin from the pancreatic islets | - Inhibit the NLRP3 inflammasome [142], decrease production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) [143]; - Inhibit AGEs-induced pro-inflammatory mediators (NO, reactive oxygen species, i-NOS) [143]; - Enhance production of anti-inflammatory cytokines (IL-10 and TGF-β) [143]. |
| Biguanides | Block the breakdown of fatty acids through activation of AMP-dependent protein kinase | Reduce glucose production in liver by decreasing gluconeogenesis and stimulating glycolysis | - Activation of AMP-activated protein kinase (AMPK) [144,145]; - Inhibit mTOR and NF-κB pro-inflammatory signaling [145]; - Reduce inflammatory cytokines IL-6 and TNF-α [146]. |
| PPAR agonists | Activate PPARα/γ/δ receptors | Enhance insulin effects, decrease insulin resistance, decrease dyslipidemia | - Downregulate the inflammatory pathway NF-κB [147]; - Regulate adipokine production and secretion [148]; - Inhibit of pro-inflammatory molecules in liver [149]. |
| α-Glucosidase inhibitors | Inhibit enzymes in the small intestine | Prevent the absorption of glucose in the intestine | - Decrease TNF-α and other inflammatory mediators [150]; - Ameliorate vascular endothelial dysfunction [151]; - Decrease C-reactive protein (CRP) [151]. |
| SGLT2 inhibitors |
inhibit SGLT-2 | Promote the excretion of glucose in the urine by inhibiting the reabsorption of glucose from the urine in the proximal tubules of the kidneys | - Improve endothelial function [12]; - Reduce inflammatory mediators IL-6, TNF-α, MCP-1, and CRP in plasma and liver [152]; - Inhibit NLRP3 inflammasome [153]; - Cause M2 macrophage polarization [153]. |
| GLP-1 agonists (GLP-1RA) | Activate GLP-1 receptor | Increase insulin secretion in a glucose-dependent manner and suppress glucagon secretion | - Reduce production of IL-6, TNF-α, and MCP-1 in adipose tissue [154]; - Inhibit NF-κB and JNK pathways [155]; - Decrease CRP [154]. |
| DPP-4 inhibitors | Inhibit DPP-4 receptor | Stimulate insulin secretion and decrease glucagon secretion, improve B-cell function and regeneration | - Reduce inflammatory cytokines IL-2, TNF-α, IL-1β, and IL-6 gene expression [156]; - Decrease NLRP3 inflammasome and TLR-4 activity [157]; - Suppress NF-κB activation [158]. |