Lec 9 - AGE/RAGE

Question 1

How is ATP generally generated?

Answer 1

GLUT2 > Glucokinase > Glycolysis

Question 2

Difference between diabetes type I and II

Answer 2

Type I :
Not enough insulin produced

Type II :
De-sensitized to insulin, reduced insulin efficacy

Question 3

What is AGE?

Answer 3

Advanced glycation end-products
e.g Glyceraldehyde

Elevated levels in diabetic patients

Question 4

What are the cellular effects of AGE?

Answer 4

Cell-surface receptor activation

Intracellular signalling response

Question 5

What is RAGE?

Answer 5

Unique receptor for AGE
Main isoform is transmembrane protein
Part of RAGE/AGE signalling pathway

Question 6

What does RAGE signalling pathway do?

Answer 6

NfKB and MAP kinase modulation
Increase RAGE expression via. NfKB activation
Highly active in diabetic patients

Cause:
Oxidative stress
Adhesion and transmigration
Vascular permeability/ blood pressure

Hence:
Induce insulin resistance

Question 7

Details on NfKB

Answer 7

Nuclear factor - KB

transcription factor composed of p50 and p65

regulates genes apoptosis, viral replication, tumorigenesis, inflammation, autoimmune disease

Inactivation by IkB

Activation result in phosphorylation and degradation of IkB

Consensus sequence of 5’ GGGACTTTCC 3’