ERS L44 - Biochemistry Basis of DM II

Question 1

Sulphonylureas: MoA

Answer 1

DM II
Act on regulatory subunit of ATP-sensitive K+ channels in beta cells.
- Stronger inhibition of this channel
- Depolarization of cell membrane
- Activation of voltage-gated Ca channel
- Ca influx –> exocytosis of vesicles with insulin

Question 2

Thiazolidinediones (TZD): MoA

Answer 2

DM II
Bind to PPAR-gamma
- increased FFA uptake by adipocytes
- Preferential differentiation of pre-adipocytes to subcutaneous rather than visceral adipocytes
- Adipocytes formed are more insulin-sensitive
- Suppress inflammatory activities –> prevent further alterations in the metabolism of adipocytes (which could lead to increased lipolysis and insulin resistance)

Question 3

Rosiglitazone

Answer 3

Thiazolidinediones (TZD) for DM II
Bind to PPAR-gamma
- increased FFA uptake by adipocytes
- Preferential differentiation of pre-adipocytes to subcutaneous rather than visceral adipocytes
- Adipocytes formed are more insulin-sensitive
- Suppress inflammatory activities –> prevent further alterations in the metabolism of adipocytes (which could lead to increased lipolysis and insulin resistance)

Question 4

Pioglitazone

Answer 4

Thiazolidinediones (TZD) for DM II
Bind to PPAR-gamma
- increased FFA uptake by adipocytes
- Preferential differentiation of pre-adipocytes to subcutaneous rather than visceral adipocytes
- Adipocytes formed are more insulin-sensitive
- Suppress inflammatory activities –> prevent further alterations in the metabolism of adipocytes (which could lead to increased lipolysis and insulin resistance)

Question 5

Biguanide: MoA

Answer 5

e.g. metformin
Activate AMP-protein kinase
- more active FFA oxidation, glycolysis, glycogenesis, etc.

Question 6

Examples of thiazolidinediones (TZD)

Answer 6

Pioglitazone
Rosiglitazone
(For DM II)

Question 7

Example of biguanide drug

Answer 7

Metformin (For DM II)