Antidiabetics

• Block ATP-sensitive potassium channels of the pancreatic β cells → depolarization of the cell membrane → calcium influx → insulin secretion

• Extrapancreatic effect: ↓ hepatic gluconeogenesis, ↑ peripheral insulin sensitivity

The use of sulfonylureas in early stages of disease can lead to a premature loss of β-cell function, potentially impairing the effectiveness of antidiabetic treatment.

·       enhances the effect of insulin

·       Reduction in insulin resistance via modification of glucose metabolic pathways

·       Inhibits mitochondrial glycerophosphate dehydrogenase (mGPD) → ↓ hepatic gluconeogenesis and intestinal glucose absorption [7]

·       Increases peripheral insulin sensitivity → ↑ peripheral glucose uptake and glycolysis

·       Lowers postprandial and fasting blood glucose levels

Reduces LDL, increases HDL

• activation of the transcription factor PPARγ (peroxisome proliferator-activated receptor of gamma type in the nucleus) →

• ↑ transcription of genes involved in glucose and lipid metabolism → ↑ levels of adipokines such as adiponectin and insulin sensitivity →

• ↑ storage of fatty acids in adipocytes, ↓ products of lipid metabolism (e.g., free fatty acids) → ↓ free fatty acids in circulation → ↑ glucose utilization and ↓ hepatic glucose production

·       Incretin effect: food intake → activation of enteroendocrine cells in the gastrointestinal tract → release of GLP-1 → GLP-1 degradation via the enzyme DPP-4 → end of the GLP-1 effect

Incretin mimetic drugs bind to the GLP-1 receptors and are resistant to degradation by DPP-4 enzyme → ↑ insulin secretion, ↓ glucagon secretion, slow gastric emptying (↑ feeling of satiety, ↓ weight)

indirectly increase the endogenous incretin effect by inhibiting the DPP-4 that breaks down GLP-1 → ↑ insulin secretion, ↓ glucagon secretion, delayed gastric emptying