diabetic cardiomyopathy Flashcards
What happens in type I diabetes
loss of beta cells in pancreas
insulin deficiency
What happens in type II diabetes
glucose uptake by insulin is reduced
more insulin production
what do most diabetic patients die from?
cardiovascular event
what are myocytes surrounded by?
collagen I matrix
Some characteristics of myofibroblasts
- ED-A fibronectin
- high contactility
- aSMA
- collagen I and III synthesis
- induced by TFG-B
is glycation enzymatic?
NO
what is a promoter of glycation in Advanced Glycation End products (AGEs)?
methylglyoxal (MGO)
Which proteins do MGO attack? What does it do?
K, R, C (thiol groups)
makes it unable to bind and activate integrin. It is not a complete inhibition. But significant enough
Which binding motif for integrin is disrupted by MGO attack?
GFOGER
also RGD
What is the consequence of MGO attack on lysine?
forms lysine crosslinking causing more crosslinking
What causes more MGO production in diabetic patients?
increased glucose uptake by glucose transporters
> cystolic hyperglycemia
> glyoxalase I turns it into methylglyoxal
How can we reduce MGO attacks?
Glyoxalase inhibitor
bromo benzyl glutathione cyclo pentyl diester
How does AGE effect collagen content?
AGE > RAGE > more growth factors > more TIMPs > less MMPs
more collagen crosslinking
what is RAGE?
Receptor for Advanced Glycation End Product
which integrin binding to collagen in GFOGER motifs is blocked by MGO?
(α1β1, α2β1, α11β1)
