Antidiabetics 2 W3 Flashcards
2 classes o ntidiabetic drugs
Act at targets involved in the control of energy metabolism in the cell
- Metformin - biguanide
- PPARy agonists
Metformin
Lowers basal and post-pradnial blood glucose conc
Mechanism doesn’t involve increased insulin secretion - wont cause hypoglycaemia
Metformin action
– Reduces gluconeogenesis in liver
– Increases peripheral glucose uptake and utilisation (skeletal muscle,
adipose tissue)
– Improves insulin sensitivity
– Reduced carbohydrate absorption from the GIT
– Decreases lipid synthesis (dual action in obesity – does not cause
weight gain; also reduces LDLs and VLDLs in blood)
Metformin pharmacological mechanisms of action
involves AMPK,
a kinase which monitors cellular energy status and is
centrally involved in energy metabolism within the cell
– Activated by increase in the AMP/ATP ratio
• As well as other actions, AMPK:
– Inhibits gluconeogenesis (liver)
– Increases glucose uptake into cells (skeletal muscle)
– Increases insulin receptor function
– Inhibits lipid synthesis
– Increases GLP-1 secretion (GIT)
Metformin Inhibits …
– Inhibits the activity of complex 1 of the respiratory chain in
mitochondria
– This means less ATP production
• [ATP]↓ [AMP]↑
– Activates AMPK
Metformin complete action
- Inhibition of complex 1,
decreasing ATP production - Increase in the AMP:ATP ratio
- Inhibition of gluconeogenesis
- Decreased ATP decreases
cAMP levels (2nd messenger
for glucagon) - Decrease in gluconeogenesis
- Activation of AMPK
- Increased breakdown of cAMP
- Decreased fat synthesis
- Increased fat oxidation
10.Decreased transcription of
genes for gluconeogenesis
PPARγ agonists Pharmacological target:
The peroxisome proliferator-activated receptor gamma (PPARγ) receptor
• PPARγ is a nuclear receptor (transcription factor)
• Found mainly in adipose tissue, but also elsewhere including liver
and skeletal muscle
• Endogenous ligands are lipids eg. fatty acids
• Together with the Retinoid X receptor, it regulates transcription
