Metabolic Effects of Insulin and Glucagon. Flashcards
What are 5 key organs that are involved in energy metabolism?
The brain.
The liver.
Adipose tissue.
Muscle tissue.
The pancreas.
What organ is involved in the most key pathways in energy metabolism?
The liver.
What organs involved in metabolic processes require the most energy?
The brain and muscles.
What metabolic organs are responsible for storing excess energy?
Adipose tissue.
How does adipose tissue store energy?
In a way that facilitates quick release of that energy.
What organ makes many of the hormones that control the various processes of energy metabolism?
The pancreas.
What are the 2 main hormones that will control the various processes of metabolism?
Insulin and glucagon.
What organ is responsible for releasing glucagon and insulin?
The pancreas.
What hormone that isn’t made in the pancreas will affect metabolism?
Epinephrine.
Where is epinephrine made?
It is made under specific conditions by the nervous system.
The metabolic processes of all the organs in energy metabolism are controlled by at least 1 of what 3 factors?
The availability of key substrates.
By hormones.
The nervous system.
What are the 2 types of cells that make up the pancreas known as?
Endocrine cells.
Exocrine cells.
Which pancreatic cells secrete their zymogens into the bloodstream?
Endocrine cells.
Insulin and glucagon are secreted by what portion of the pancreas?
The endocrine portion.
Where will the exocrine cells of the pancreas release their products or zymogens to?
Into the pancreatic duct where they will enter the lumen of the small intestine.
What makes up the endocrine portion of the pancreas?
Islets of Langerhans.
Where are the islets of Langerhans found in the pancreas?
They surround blood vessels and are embedded in the exocrine portion of the organ.
Islets of Langerhans cells account for what percentage of all pancreatic cells?
1-2%.
Islets of Langerhans are made up of what 3 cell types?
Alpha.
Beta.
Delta.
What are the alpha cells of the islets of Langerhans responsible for?
They are responsible for secreting glucagon.
What are the beta cells of the islets of Langerhans responsible for?
They will secrete insulin and amylin.
What are the delta cells of the islets of Langerhans responsible for?
They secrete somatostatin.
What will usually induce the release of insulin from the pancreas?
A meal.
How long after a meal has been consumed will there be a rise in blood glucose levels?
Around 10 minutes.
What will a rise in blood glucose levels trigger?
A release of insulin.
What glucose transporters will bring glucose in to the pancreas?
GLUT-2 transporters.
What enzyme is triggered by the entry of glucose into the pancreas?
Glucokinase.
What metabolic process is triggered by the entry of glucose into the pancreas?
Insulin stimulates glycolysis which causes a rise in ATP across the body.
How will the presence of glucose in the cytoplasm of beta cells trigger the release of insulin?
Its presence closes a potassium channel in the plasma membrane.
This causes a depolarisation of the plasma membrane, allowing calcium to enter the cytoplasm.
Cytoplasmic calcium allows insulin vesicles to fuse to the cell membrane so they can be released.
How many chains make up an insulin molecule?
2 chains.
What links the 2 chains that make up insulin together?
2 intermolecular disulphide bonds.
What are the 2 chains that make up insulin called?
The A and the B chain.
Are there any intramolecular bonds in the insulin molecule?
Yes.
The A chain contains 1 intramolecular disulphide bond.
What are the monomers that make up insulin?
Amino acids, so it is effectively a protein.
Are the disulphide bridges important for the structure and behaviour of insulin?
Yes.
The hormone will not work without them.
How is insulin synthesised?
As a much larger protein that contains an additional C chain and a leader or signal terminus at the amino end.
What is newly synthesised insulin known as?
Preproinsulin.
Where is insulin synthesised?
In the endoplasmic reticulum of beta cells.
What does the signal terminus of preproinsulin allow for?
The secretion of insulin from the ER into the lumen of the ER.
What happens to preproinsulin once it is in the lumen of the ER?
The signal terminus is removed.
What molecule is formed when the signal terminus is removed from preproinsulin?
Proinsulin.
What is proinsulin made up of?
The A chain.
The B chain.
The C chain.
What happens once proinsulin has been formed?
The disulphide bridges are formed between the A and B chain.
What happens as proinsulin moves through the lumen of the ER?
It is packaged into golgi vesicles, where the C chain is removed and insulin is formed.
What happens to the C chain once it is removed from proinsulin?
It is secreted from the body in urine.
What happens to the signal terminus of preproinsulin?
It is recycled in the ER.
What activates insulin synthesis?
Glucose in the blood (activates glucokinase in β cells).
Amino acids in the blood (especially arginine).
Secretin from the intestine (response to food intake).
What inhibits insulin synthesis?
Scarcity of food.
Epinephrine.
How will insulin travel to cells throughout the body?
Through the bloodstream.
What receptors will insulin bind to on cells?
Insulin receptors.
How many subunits does the insulin receptor have?
4.
Where are the subunits of the insulin receptor located on the cell?
2 alpha subunits on the extracellular side.
2 beta subunits on the cytoplasmic side.
What are the 4 subunits of an insulin receptor?
2 alpha subunits.
2 beta subunits.
Will an insulin receptor recognise any other molecules other than insulin?
No.
It only recognises insulin.
What portion of an insulin receptor will insulin bind to?
The alpha portion.
What happens when an insulin molecule binds to the alpha portion of an insulin receptor?
It will elicit changes in the the beta portion.
When is the beta subunit of an insulin receptor activated?
When insulin binds to the alpha subunit.
What changes will the beta subunit carry out once insulin binds to the alpha subunit of an insulin receptor?
The beta subunit will phosphorylate a tyrosine kinase which will phosphorylate other proteins leading to a cascade of intracellular responses.
What will the intracellular responses that are induced by insulin lead to?
To increased glucose uptake.
When blood glucose levels are high, what cells will take up a large amount of glucose?
Muscle and adipose cells.
Will gene transcription also lead to glucose uptake?
Yes.
It will lead to an up regulation or down regulation of specific enzymes such as PFK-2.
Will insulin phosphorylate or de-phosphorylate enzymes?
Insulin will de-phosphorylation enzymes.
The phosphorylation of enzymes by insulin will lead to the inhibition of what processes?
Glucose producing processes such as gluconeogenesis.
The phosphorylation of enzymes by insulin will lead to the activation of what processes?
Glucose consuming pathways such as glycolysis.
How is the insulin receptor de-activated?
By the de-phosphorylation of tyrosine kinase.
Are the any 2nd messengers involved in insulin signals?
No.
Which tissues are particularly sensitive to insulin?
Muscle and adipose tissues.
Why are muscle and adipose tissues particularly sensitive to insulin?
So they can pick up glucose for energy needs, glycogen synthesis or energy storage.
How does type-1 diabetes affect glucose uptake?
It reduces the uptake of glucose into muscle and fat cells which results in the person becoming hyperglycaemic.
What are insulin effectors?
Molecules that can be phosphorylated by phosphorylated tyrosine residues to produce a cellular cascade.
What are 3 insulin effectors?
One of the 4 insulin receptor substrates (IRS).
Adaptors.
Enzyme effectors.
What are 7 common cellular responses to insulin?
Specific gene expression.
Protein synthesis.
Up regulation of enzymes.
Regulation of transcription.
Activation of GLUT-4 transporters in muscle and adipose tissue.
Increased glucose uptake in muscle and adipose tissue.
Activation of enzymes by covalent modification.
What 2 processes activate the insulin receptor?
Insulin binding to the receptor.
By auto-phosphorylation.
What inhibits the insulin receptor?
De-phosphorylation of the tyrosine kinase residue.
Which insulin sensitive cells will use facilitated glucose transport?
Most tissues.
Which insulin insensitive cells will use active glucose transport?
Epithelia of the intestine.
Renal tubules.
Choroid plexus.
Which insulin insensitive cells will use facilitated glucose transport?
Erythrocytes.
Leukocytes.
Lens of eye.
Cornea.
Liver.
Brain.
Are insulin sensitive cells activated by the presence of insulin in diabetics?
No.
Is insulin an anabolic or catabolic hormone?
Anabolic.
Why is insulin considered to be an anabolic hormone?
It will stimulate the synthesis of;
Glycogen from glucose.
Proteins from amino acids.
TAGs from fatty acids.
What processes will insulin inhibit?
Gluconeogenesis.
Glycogenolysis.
Lipolysis.
The consumption of carbohydrates will inhibit which pathways in the liver?
Gluconeogenesis and glycogenolysis.
The consumption of carbohydrates will activate which pathways in the liver?
Glycogenesis and glycolysis.
The consumption of carbohydrates will activate which pathways in the muscle?
Glycogenesis and glycolysis.
Does the liver ever use GLUT-4 transporters?
No.
What transporters bring glucose from the bloodstream into the liver?
GLUT-2 transporters.
What will adipose tissue use glucose for?
To synthesise dihydroxyacetone which is converted to glycerol phosphate which is the backbone for TAGs.
What do GLUT-4 transporters do?
They bring glucose from the blood into muscle and adipose tissue.
What do GLUT-2 transporters do?
They bring glucose from the blood into the liver.
What hormone will insulin inhibit in adipose tissue?
Hormone sensitive lipase.
What will the inhibition of hormone sensitive lipase result in?
The inhibition of TAG synthesis.
What will increased glucose uptake in adipose tissue result in?
Increased levels of glycerol-3-phosphate and DHAP which will increase TAG synthesis.
What enzyme in the endothelial cells will increase due to the presence of insulin?
Lipoprotein-lipase.
What is the job of lipoprotein lipase?
It will break down chylomicrons and VLDL to release fatty acids.
What effects will insulin have on protein uptake in various tissues?
In increased uptake of amino acids which results in increased protein synthesis.
Will the liver, muscle or adipose tissue experience increased glucose uptake as an effect of insulin?
Liver. No.
Muscle. Yes.
Adipose. Yes.
Will the liver, muscle or adipose tissue experience increased cellular respiration as an effect of insulin?
Liver. Yes.
Muscle. Yes.
Adipose. Yes.
Will the liver, muscle or adipose tissue experience increased glycogenesis as an effect of insulin?
Liver. Yes.
Muscle. Yes.
Adipose. No.
Will the liver, muscle or adipose tissue experience an inhibition of glycogenolysis as an effect of insulin?
Liver. Yes.
Muscle. Yes.
Adipose. No.
Will the liver, muscle or adipose tissue experience increased amino acid uptake as an effect of insulin?
Liver. No.
Muscle. Yes.
Adipose. No.
Will the liver, muscle or adipose tissue experience a stimulation of protein synthesis as an effect of insulin?
Liver. Yes.
Muscle. Yes.
Adipose. Yes.
Will the liver, muscle or adipose tissue experience a inhibition of protein degradation as an effect of insulin?
Liver. Yes.
Muscle. Yes.
Adipose. Yes.
Will the liver, muscle or adipose tissue experience a stimulation of fatty acid and TAG synthesis as an effect of insulin?
Liver. Yes.
Muscle. No.
Adipose. Yes.
Will the liver, muscle or adipose tissue experience a inhibition of lipolysis as an effect of insulin?
Liver. Yes.
Muscle. No.
Adipose. Yes.
Will the liver, muscle or adipose tissue experience an up regulation of lipoprotein lipase as an effect of insulin?
Liver. No.
Muscle. No.
Adipose. Yes.
What cells will release glucagon?
The alpha cells of the islets of Langerhans in the pancreas.
When is glucagon released into the blood?
When blood glucose levels are low.
How is insulin synthesised?
It is made as a much larger protein which is then modified to give glucagon.
How many amino acids make up glucagon?
29 amino acids.
What organ in the body will sense a drop in blood glucose levels?
The hypothalamus of the brain has glucose sensors which will sense a drop in blood glucose.
When will glucagon be produced?
When blood glucose drops to around half its normal level.
What happens once blood glucose levels drop to around half of their usual level?
The hypothalamus sends signals to the pancreas to stop producing insulin and to start producing glucagon and norepinephrine?
When will epinephrine be produced in the well fed state?
During stressful situations or during intense exercise.
How is cortisol produced in the fasting state or in the well fed state?
The hypothalamus sends signals to the pituitary to produce ACTH which leads to the production of cortisol.
What does the release of cortisol stimulate?
The release of norepinephrine and activates PDP carboxykinase.
What 4 steps does cortisol use to stimulate genetic changes?
It travels into the cytoplasm and will bind to a specific receptor to form the activated complex.
The activated complex travels into the nucleus and binds to an enhancer region of DNA.
It then finds a specific gene and activates the promoter region of that gene.
The gene will then make more mRNA which is translated into enzymes.
Can glucagon cause glycogenolysis and gluconeogenesis on its own?
Yes.
What will cause the release of epinephrine, norepinephrine and cortisol?
Stressful situations, such as fight or flight scenarios and extreme exercise.
Will epinephrine, norepinephrine and cortisol inhibit the synthesis of glucose storage products in the well fed state?
Yes.
They will initiate the breakdown of glycogen stores etc.
What activates glucagon synthesis?
A decrease of blood glucose.
An increase in amino acids in the blood after a protein rich meal.
An increase in epinephrine or norepinephrine.
What inhibits glucagon synthesis?
High glucose.
Insulin.
Food intake in the form of carbohydrates.
What kind of receptors do glucagon receptors tend to be?
GPCRs.
What 2 systems can a GCPR activate?
The adenylate cyclase system.
Thephosphoinositide system.
When is the adenylate cyclase system activated?
When a stimulus binds to a GPCR.
What stimulus will activate the adenylate cyclase system?
Epinephrine.
Norepinephrine.
Glucagon.
Will epinephrine and glucagon activate the adenylate cyclase system from the same receptors?
No.
Glucagon uses a glucagon receptor and epinephrine uses the beta-adrenergic receptor and glucagon but they activate the same pathway.
The glucagon receptor and beta-adrenergic receptor are what kind of receptors?
GCPRs.
What is the 2nd messenger in the adenylate cyclase system?
Cyclic AMP (cAMP).
What is step 1 of the adenylate cyclase system?
A hormone binds to the extracellular side of the membrane and this will activate the GPCR.
What is step 2 of the adenylate cyclase system, once the GCPR has been activated?
The GPCR relays the message to the G protein in the cytoplasm.
The alpha subunit of the G protein is bound to GDP and once activated by the signal, the GDP will be replaced with GTP.
How many subunits make up the G protein that is used in the adenylate cyclase system?
3 subunits.
Alpha.
Beta.
Gamma.
When the GDP of the G protein in the adenylate cyclase system is replaced with GTP, what does it become known as?
The GS-alpha subunit.
What happens in step 3 of the adenylate cyclase system, once the G protein is bound to GTP?
The GS-alpha subunit dissociates from the beta and gamma subunits and moves to the target enzyme and bind activate it it.
What is the target enzyme of the GS alpha subunit?
Adenylate cyclase.
What happens in step 4 of the adenylate cyclase system, once adenylate cyclase has been activated?
Adenylate cyclase uses an ATP to catalyse the formation of cAMP which is the 2nd messenger.
What happens in step 5 of the adenylate cyclase system, once cAMP has been formed?
cAMP will then travel through the cytoplasm to activate protein kinase A.
What happens in step 6 of the adenylate cyclase system, once PKA has been activated by cAMP?
PKA will phosphorylate and activate other enzymes within the cell. This is when a cellular response is produced.
What part of the adenylate cyclase system produces a cellular response?
The phosphorylation of enzymes by PKA.
How is the adenylate cyclase system stopped?
Phosphodiesterase will hydrolyse cAMP to 5-AMP and PKA will be deactivated.
What is the stimulus for the beta adrenergic receptor?
Epinephrine/norepinephrine.
What is the G protein for the beta adrenergic and glucagon receptor?
GS alpha.
What is the effector enzyme for the beta adrenergic and glucagon receptor?
Adenylate cyclase.
What is the second messenger for the beta adrenergic and glucagon receptor?
cAMP.
What is the second messenger target for the beta adrenergic and glucagon receptor?
Protein kinase A.
What is the stimulus for the glucagon receptor?
Glucagon.
Is the alpha-1 adrenergic receptor is distinct from the beta adrenergic receptor?
Yes.
What do the alpha-1 adrenergic receptor and the beta adrenergic receptor have in common?
They are both GCPRs.
What activates the alpha-1 adrenergic receptor?
Epinephrine or norepinephrine.
What is the major difference between the beta adrenergic receptor and the alpha-1 adrenergic receptor?
The alpha-1 adrenergic receptor activates a different G-protein which activates a different target enzyme and produces a different 2nd messenger.
What pathway is activated by the alpha-1 adrenergic receptor?
The phosphoinositide system.
What is the phosphoinositide system called the phosphoinositide system?
Because it uses phosphoinositol 4,5-bisphosphate, this can be abbreviated to PIP-2.
Where is PIP-2 found?
As part of the plasma membrane.
What will cleave PIP-2?
Phospholipase C.
What is formed when PIP-2 is cleaved?
IP3 and DAG.
What is step 1 of the phosphoinositide system?
Epinephrine or norepinephrine binds to the alpha-1 adrenergic receptor and will signal the G protein.
What is step 2 of the phosphoinositide system once epinephrine has bound to the receptor?
The alpha subunit of the G protein is swaps GDP for GTP.
The alpha subunit then dissociates from the G protein.
What is the dissociated alpha subunit known as in the phosphoinositide system?
GQ alpha.
When does the GQ alpha subunit become activated?
When it is bound to GTP.
What is step 3 of the phosphoinositide system once the GQ alpha subunit has dissociated from the G protein?
GQ alpha travels to its target enzyme which is phospholipase C.
What is step 3 of the phosphoinositide system once phospholipase C has been activated?
Phospholipase C travels through the cell membrane until it finds PIP-2.
What happens when phospholipase C cleaves PIP-2?
It cleaves it to form 2 second messengers which are IP3 and DAG.
What does IP3 do in the phosphoinositol system?
It travels into the cytoplasm and binds to the ER which causes a release of calcium ions from the ER.
What does DAG do in the phosphoinositol system?
DAG and the calcium ions from the ER will activate protein kinase C.
Are the calcium ions in the phosphoinositol system considered to be a 2nd messenger?
Yes.
What does protein kinase C do once it is activated by the phosphoinositol system?
It will phosphorylate specific enzymes which leads to a cellular response.
What is the stimulus for the alpha-1 adrenergic receptor?
Epinephrine/norepinephrine.
What is the G protein for the alpha-1 adrenergic receptor?
GQ alpha subunit.
What is the effector enzyme for the alpha-1 adrenergic receptor?
Phospholipase C.
What is the effector enzyme target for the alpha-1 adrenergic receptor?
PIP-2.
What are the 2nd messengers for the alpha-1 adrenergic receptor?
Calcium ions.
DAG.
IP-3.
What is the 2nd target in the alpha-1 adrenergic receptor?
Protein kinase C.
Will epinephrine and glucagon be produced when blood glucose levels are low?
Yes.
What pathways are shut down by the presence of glucagon?
The major pathways that utilise glucose such as glycolysis.
What pathways are activated by the presence of glucagon?
The pathways that synthesise glucose within the body such as glycogen degradation and gluconeogenesis.
Glucagon prompts the release of energy from where?
From energy that is already in the body.
Is glucagon an anabolic or catabolic hormone?
A catabolic hormone.
What hormone activates lipolysis?
Glucagon.
Does glucagon stimulate amino acid uptake in cells?
Yes.
Where are the amino acids that are taken up by cells as a response to glucagon taken from?
The turnover of proteins in the muscle
What are the amino acids that are taken up by cells as a response to glucagon used for?
They are used as gluconeogenic precursors.
What will happen to stored carbohydrates in the fasting state?
The liver will break them down to release glucose via gluconeogensis.
What happens to lipids in the fasting state?
Glucagon leads to TAG breakdown in the liver and will also stimulate the β oxidation of fatty acids and ketone synthesis.
What cells does beta oxidation take place in?
In cells that have mitochondria.
What happens to proteins in the fasting state?
There will be an increase in amino acid uptake from muscle degradation.
Will the amount of amino acids in the blood decrease in the fasting state?
Yes.
As they are being used as precursors for gluconeogenesis.
What amino acid is most often used as a gluconeogenic pre-cursor?
Alanine.
Will glucagon stimulate glycogenolysis in the liver, muscle or adipose tissue?
Liver. Yes.
Muscle. No.
Adipose tissue. No.
Will glucagon inhibit glycogenesis in the liver, muscle or adipose tissue?
Liver. Yes.
Muscle. No.
Adipose tissue. No.
Will glucagon stimulate gluconeogenesis in the liver, muscle or adipose tissue?
Liver. Yes.
Muscle. No.
Adipose tissue. No.
Will glucagon stimulate lipolysis in the liver, muscle or adipose tissue?
Liver. Yes.
Muscle. No,
Adipose tissue. Sometimes, but this is due to epinephrine.
Will glucagon stimulate of ketone formation in the liver, muscle or adipose tissue?
Liver. Yes.
Muscle. No.
Adipose tissue. No.
Will glucagon stimulate of amino acid uptake in the liver, muscle or adipose tissue?
Liver. Yes.
Muscle. No.
Adipose tissue. No.
When will someone become hypoglycaemic?
If blood glucose levels drop below half their usual concentration.
What is around 1/2 the normal blood glucose concentration?
Around 40 mg/dl.
How many sets of symptoms are associated with hypoglycaemia?
2.
How can hypoglycaemia be resolved?
By the administration of glucose to the affected person.
What are the 1st set of symptoms of hypoglycaemia called?
The adrenergic symptoms.
What are the adrenergic symptoms of hypoglycaemia?
Increased anxiety.
Body tremors etc.
The adrenergic symptoms of hypoglycaemia are considered to be a normal response to what?
A drop in blood glucose.
What can cure the adrenergic symptoms of hypoglycaemia?
By the brain releasing glucagon which will lead to an increase of blood glucose levels.
When will the brain start to release glucagon?
When blood glucose levels reach between 70-60 mg/dl.
What are the 2nd set of symptoms of hypoglycaemia called?
The neuroglycopenic symptoms.
What are the neruoglycopenic symptoms of hypoglycaemia?
An impairment of brain function.
Headaches.
Can result in a coma if left untreated.
What is are the more serious symptoms of hypoglycaemia?
The neuroglycopenic symptoms.
What causes the neuroglycopenic symptoms of hypoglycaemia?
When the brain does not register a drop in blood glucose levels and no glucagon is produced.
What are 4 other factors other than low blood sugar that can induce hypoglycaemia?
Insulin induced.
Postprandrial.
Fasting.
Alcohol intoxication.
What is insulin induced hypoglycaemia?
When a diabetic takes insulin and forgets to eat.
The insulin stimulates an uptake in glucose from the blood resulting in hypoglycaemia.
What is postprandial hypoglycaemia?
When the pancreas over produces insulin after a meal.
This causes glucose in the blood to be removed and hypoglycaemia occurs.
What is fasting hypoglycaemia?
When blood glucose drops below normal levels due to no food being consumed.
It can also occur via a disease, where the pancreas has a tumour that causes a production of insulin.
What is alcohol intoxication hypoglycaemia?
Alcohol metabolism causes an NADH surplus which deprives the liver of precursors for gluconeogenesis.
If gluconeogenesis cannot occur, then hypoglycaemia will set in.
What enzyme metabolises alcohol?
Alcohol dehydrogenase.
What does alcohol dehydrogenase convert ethanol to?
Acetaldehyde which is converted to acetate by acetaldehyde dehydrogenase.
What is does acetaldehyde and alcohol dehydrogenase produce in alcohol metabolism?
NADH.
What happens to blood glucose levels and glucagon levels immediately after a meal?
Blood glucose levels rise and glucagon levels will rise with them.
What causes glucagon levels to rise after a meal?
Amino acids in the blood.
When will glucagon levels fall after a meal has been consumed?
When insulin levels rise.
