Table 3 Targets and mechanisms of hypoglycemic agents
From: Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy
Medicines | Target organs | Action target | Mechanisms of hypoglycemia |
|---|---|---|---|
Metformin | Liver, muscle adipose | Modulate mitochondrial enzymes and hepatic redox state, and increases cellular AMP kinase | ↓hepatic gluconeogenesis; ↑glucose uptake |
SUs | Pancreatic islet β cell | Bind to SUR-1 subunit of the K-ATP channels, leading to channel closure and membrane depolarization | ↑insulin secretion |
Meglitinides or glinides | Pancreatic islet β cell | Bind to SUR-1 subunit of the K-ATP channels, leading to channel closure and membrane depolarization | ↑insulin secretion |
AGI | Intestine | Inhibit α-glucosidase in the small intestinal brush border | ↓absorption of complex polysaccharide |
TZD | Muscle, adipose | Activate PPAR-γ to increase adiponectin and GLUT-4 expression while inhibiting TNF-α effect in adipocytes | ↑fatty acid uptake and storage; ↓fat accumulation in the liver, muscle, and pancreas; ↑glucose uptake |
DPP-4i | Pancreatic islet α/β cell | Block degradation of incretin hormones (GLP-1 and GIP) by the enzyme DPP-4 and increase incretin hormones levels | ↑insulin secretion; ↓glucagon secretion |
GLP-1 | Pancreatic islet α/β cell | Resistant DPP-4 to extend the half-life of GLP-1 simulate GLP-1 receptor along with “supra-physiologic” GLP-1 levels | ↑insulin secretion; ↓glucagon secretion |
SGLT-is | Kidney, intestine | Block SGLT-1 in intestine or/and SGLT-2 in kidney receptors and lower the renal threshold for glycosuria | ↓intestinal or/and renal glucose reabsorption |
