4. Insulin counter-regulatory hormones Flashcards
Describe post-prandial metabolism and the processes that normally occur following a meal
After a meal there is a rise in blood glucose and this causes the release of insulin from the beta cells in the islets of langerhan of the pancreas
The release of insulin stimulates glucose uptake into the muscles and adipocytes via translocation of GLUT4 to the plasma membrane
Insulin stimulates glycogen synthesis in muscles from the glucose that has entered
Insulin inhibits lipolysis (breakdown of triglycerides into fatty acids) via inhibition of hormone sensitive lipase
Insulin stimulates lipogenesis
Insulin also inhibits gluconeogenesis (amino acids are the substrate for this)
Describe the insulin levels whilst fasting
During fasting, there is a fall of insulin and so all the processes that were inhibited by insulin are now reversed and activated e.g. lipase is no longer inhibited and so lipolysis occurs
Where is glucagon produced and describe the structure of glucagon
Produced by the alpha cells of the islets of Langerhans
Peptide made up of 29 amino acids
Give a brief overview of the production of glucagon
The synthesis of glucagon is very similar to that of insulin
Preproglucagon is cleaved to form proglucagon
Proglucagon is then also cleaved to form glucagon and this is then stored within a vesicle ready for release
What factors stimulate the release of glucagon?
Blood glucose concentration if they fall below 3mm/L
Increased blood amino acids - especially alanine and arginine (the glucagon promotes rapid conversion of amino acids into glucose
Exercise stimulates the release of glucagon
Describe the structure of the glucagon receptor
Glucagon receptor is a G-protein coupled receptor that spans across the membrane seven times
When glucagon binds to this, adeno-cylase is activaed and cAMP is released - this then goes on to activate different kinases e.g. protein kinase A
This leads to increased levels of glycogenolysis
Describe the metabolism that occurs during prolonged starvation in terms of glucagon
SO the inhibition of insulin is no longer present so lipolysis occurs
The liver also stimulates gluconeogenesis via the usage of amino acids and glycerol from protein degradation and lipolysis
Glucagon is released and this stimulates the breakdown of glycogen from the kidneys and so leads to a release of glucose into the bloodstream (glycogenolysis) and this can be used by the muscles
Lipolysis is stimulated and this leads to a production of glycerol and fatty acids - the fatty acids can be used (oxidated) by most tissues for the production of ATP so they no longer need to use glucose - the glucose then remains for use by the brain
Once fatty acid stores deplete, the liver uses amino acids from the muscle to produce more fatty acids SO breakdown of muscle
Ketogenesis then also starts to occur where acetyl coA (from beta oxidation of fatty acids) is converted to ketone bodies which can be used by the brain for ATP synthesis
Ketone bodies become the main sources of fuel
How are the levels of glucagon in the blood regulated?
The secretion is inhibited by insulin and by somatostatin so when one of these is active, glucagon production is switched off
Insulin also stops the production of cAMP so the glucagon cannot have the desired effect when it binds to the receptor
What are catecholamines and their role?
These are adenocortical hormones
Released in response to stress
e.g. adrenaline and noradrenaline
Adrenaline essentially works in the same way as glucagon - functions on top of glucagon and activates the exact same processes
What are gucocorticoids and their role?
These are steroid hormones which use cholesterol as the basis of their production
Released in response to certain hormones from the pituitary
Can activate the translocation of certain proteins
This has a much longer term effect than insulin and glucagon
e.g. cortisol
Enhances gluconeogenesis
Inhibits glucose uptake
Stimulates lipolysis
Helps to maintain the blood pressure
What is the growth hormone and what is it’s role?
Hormone that stimulates growth
Increases lipolysis
Reduces glucose uptake
What other hormones are involved with metabolism?
Thyroid hormones - work very similarly to cortisol
Incretins - GI hormones
GLP-1 - come from the same precursor as glucagon
