Diabetes Flashcards
What makes up the starve feed cycle?
STARVE- Feed cycle
* The daily cycle of feeding passes through a series of states
* Fed (postprandial) state (0-4 hours after a meal)
* Early post-absorptive state (4-16 hours after a meal
* Late post.-absorptive (early fasting up to 3 days after meal)
* Refed state
What cells release insulin
B cells of pancreas
What do hepatocytes do when there is an increase in glucose levels Kidney
Increase glycogen is synthesis
Converted glucose into fatty acids from adipocytes
What are the two key tissues for glucose uptake?
Liver and skeletal muscle
What are the transported involved in glucose uptake?
Glucose uptake
* Glucose uptake brought about by facilitated diffusion
* Family of transporters known as GLUT (tissue specific)
* GLUT3 (brain, nerve tissue) Low Km allows a relatively constant rate of glucose uptake
* GLUT2 (liver, B cells pancreas) high Km rate of uptake proportional to extracellular glucose concentration
* GLUT2 doesnt take up much glucose when at low levels but when glucose conc is higher- take up majority of glucose
What transports fatty acids to tissues? And what how are they taken up?
Chylomicrons transport fatty acids. Taken up by activation of lipoprotein lipase (ApoC-II)
What happens during the early post absorptive state?
Early post-absorptive state
* Glucose level begin to fall because of ongoing utilisation triggering the release of glucagon
* Initially hepatic glycogenolysis maintains blood glucose levels (major source up to 16 hours) also lipolysis is initiated releasing fatty acids from adipocytes
What happens during the late post- absorptive state?
• Over time body becomes more reliant on hepatic gluconeogensis for maintenance of blood glucose as hepatic glycogenolysis maintains becomes depleted
• Cortisol release due to increased stress haas similar effect as glucagon, except binds to muscle tissues to increase protein degradation
• Glucagon/ cortisol as well as binding to hepatocytes also stimulate the release of fatty acids from adipocytes
• Fatty acids are exported to liver and other tissues for fuel - Glucose spared for the brain use
What happens after 2-3 days of starvation?
The brain switches to utilise ketone bodies as bodies as the main source of fuel 70-80%
Allows reduction in gluconeogensis (protein sparing) and stabilisation of glucose levels.
Kidney becomes a major gluconeogenic tissue
When fat stores are exhausted protein is metabolised once more causing irreversible damage to organs
What are the diseases affecting fuel utilisation?
Diseases affecting fuel utilisation
* Defects in glycogen metabolism- hypoglycaemia
* Defects in fatty acids oxidation - hypoglycaemia
* Diabetes mellitus- Hyper glycemic and hypo
What are major contributing factors to type 2 diabetes?
Age, Obesity and Ethnicity
Describe obesity as a risk factor
Become tolerate to glucose load- result in insulin resistance- and B cell dysfunction
Obesity results in ectopic storage of lipids (e.g liver and SKM) and activation of inflammatory pathways- lead to insulin resistance
What is type 2 diabetes?
Insulin doesn’t work- has blunted response by targeting tissue to insulin even though its secreted in normal and supra normal amounts- insulin resistance
What is type 1 diabetes caused by
absolute failure of B cells of the pancreas to produce insulin.
When can insulin resistance occur?
When can insulin resistance occur?
Pre-receptor resistance- Insulin autoantibodies, mutant insulin structure, insulin secretion defects
Receptor resistance- decreased number, decreased affinity (altered strucuture) . Impaired recpetor tyrosine kinase activity, blocking antibodies
Post receptor resistance- post receptor signalling e.g IRS01, PIP3-kinase, AKt) Down regulation of GLUT4
What is insulin resistance post receptor insulin resistance?
Insulin resistance
Post receptor insulin resistance
* Tumour necrosis Factor (TNFa) is secreted from adipocytes, particularly visceral dipocutes
* In obesity there is increased secretion of TNFa
* TNFa inhibits IS-1 activation (by insulin)
* Thus insulin-signal transduction is inhibited (insulin resistance)
* Reduced glycogen synthesis and reduced GLUT4 transport to PM (skeletal muscle)
* Insulin resistance leds to hyperglycaemia
What is the role of Adiponectin?
- Adiponectin is a hormone secreted by adipose tissue that circulate in the blood
- Adiponectin acvitates signalling cascades that eventually increase glucose uptake by muscle, increase atty acid oxidation by muscle and liver, and decrease gluconeogensis in the liver
- Increased TNF in obesity reduces plasma Adiponectin levels
- Decreased Adiponectin in obesity leads to increased plasma FAs and glucose- leads to insulin resistance and hyperglycaemia
What is the strongest and most consistent predictor of type 2 diabetes?
• biochemically the strongest and most consistent predictor of T2SM
• Polymorphisms in Adiponectin gene (SNP 276 and SNP45) are linked to plasma levels of Adiponectin, insulin resistance and T2DM
• IF HAVE mutation more likely to have more insulin resistance so type 2 - this alone does not make you- just increases
What is the role of genetics in type 2 diabetes?
Fault GLUT2/ K channel
Faulty insulin synthesis release or storage
Faulty pre-receptor, recepto or post receptor signalling
What is type 2- non insulin dependent diabetes?
- Late onset diabetes
Insulin low normal or high but has a blunted response- results in insulin resistance - subacute onset- may take months, years and be asymptomatic
