Diabetes Disease Mechanisms Flashcards
What occurs in protein glycation?
Glucose combines with protein amino groups, no enzymes required
Effects of protein glycation
Gives proteins abnormal function so may result in disease
Common examples of protein glycation
- glycated collagen in artery walls traps LDLs
* Glycation of cel surface receptors increases production of pro-inflammatory cytokines
Polyol pathway disruption process
- Increased cytoplasm glucose conc.
* Excess glucose metabolised to sorbitol which is converted to fructose
Effects of Polyol pathway disruption
- Increased osmolality so water influx, swelling and impaired function
- NADPH consumed so oxidative stress
Effects of Protein Kinase C activation
- VEGF production so new blood vessel growth
- Increased pro-inflammatory cytokine production
- Increased endothelin-1 and decreased NO production
2 categories of diabetic cardiovascular disease
- Macroangiopathy (atheroma)
* Microangiopathy (thicker basement membrane with leaky vessels, also affects glomerulus)
Effects on peripheral tissues
Ischaemia of peripheral tissues leads to gangrenous necrosis
Effects on peripheral nerves
Microangiopathy, protein glycation, Polyol pathway disruption in Schwann cells and neurons causes diabetic neuropathy
Diabetic cataract details/cause
- cloudiness of crystalline lens
* excess sorbitol production
Diabetic glaucoma cause
- increased VEGF causes increased number of vessels
* results in impaired aqueous humour drainage
Diabetic retina cause
- Increased capillary permeability causes oedema and haemorrhages
- resulting hypoxia causes increased number of vessels to form, under VEGF influence
3 mechanisms of glycaemic injury
- Protein glycation
- Polyol pathway disruption
- Protein kinase C activation
