012 Molecular Defecits in Diabetes Mellitus Flashcards
What are the 3 targets of autoimmune islet cell antibodies?
Tyrosine phosphatase
Gluamic acid decarboxylase
Insulin 51 aa
Which HLA is most associated with Beta cell autoimmunity?
HLA DR3/4 DQ8
What is the T1DM 3/4 genotype?
DQA 301/ DRB 401
How does high level of insulin affect androgen production?
Increases androgen production
How does insulin affect the autonomic system?
Increases sympathetic syndrome
What is fanconi - Bickel syndrome?
Mutations in GLUT2 causing inability for beta cells to take up insulin -> post prandial hyperglycaemia and reduced insulin levels.
Where is IRS1 important?
In the muscles
Where is IRS2 important?
Important in the pancreas for secretion of insullin
How do NEFA’s and DAG’s as well as inflammatory mediators from adipose tissue affect IRS1 and IRS2 receptors?
Increase serine phosphorylation of IRS1 and IRS2, inhibiting ability to stimulate metabolism and growth in the normal way.
How do high insulin levels affect IRS1 and IRS2 receptors?
Degredation of both IRS 1 and IRS2
Which type of MODY is most prominent?
MODY 3
What is MODY 1
Mutation of HNFalpha4 –> insulin slowly declines with time
What is MODY 2
Mutation with glucokinase, affecting glucose sensing in pancreas –> impaired from birth
What is MODY 3
Mutation of HNFalpha1 –> insulin slowly declines with time
What is MODY 4
Mutation with PDX1 transcription factor
