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.
