The Endocrine Pancreas- insulin, glucagon and somatostatin Flashcards
When insulin dominates over glucagon, are we in an anabolic or catabolic state?
Anabolic
Which type of hormone is insulin?
Peptide hormone
Which cells produce insulin?
Pancreatic beta cells
Insulin is synthesised as a preprohormone known as preproinsulin which is then converted into proinsulin in the ER.
What happens to proinsulin next?
Packaged as granules into secretory vesicles.
Within the granules, proinsulin is cleaved to form insulin and C-peptide.
Instead of measuring insulin levels in a diabetic patient, what would you measure?
C-peptide levels
-> patient could be injecting insulin so measuring this instead indicates endogenous pancreatic beta cell function
An increase in BG levels stimulates the release of insulin. What else can trigger the release of insulin?
Increase in amino acids
How can excess glucose be stored?
As glycogen in the liver and muscle
As triacylglycerol’s in liver and adipose tissue
Amino acids can be used as an energy source but aren’t usually unless in what state?
State of starvation
->excess amino acids stored as fat btw h.e. flashback xox
The mechanism by which insulin is released depends on the activity of what?
The potassium ATP channels on the pancreatic beta cells
When glucose is in abundance, how does it enter cells?
Via GLUT
As glucose enters cells via GLUT, metabolism increases.
What happens when metabolism increases?
ATP increases within cells and the potassium ATP channel closes
What happens after the ATP potassium channels close?
Intracellular potassium rises which depolarises the cell.
Voltage gated calcium channels open and trigger insulin exocytosis into circulation
->wordy but read through, should hopefully make sense
Describe the mechanism of control of insulin.
(basically the last two flashcards together to give you the whole story)
Glucose enters cells via GLUT, metabolism increases.
ATP increases and ATP potassium channels close.
Intracellular potassium increases and depolarises the cell.
Voltage gated calcium channels open and trigger the exocytosis of insulin into the circulation.
What is the primary action of insulin?
Lower blood glucose
How does insulin lower blood glucose?
Binds to tyrosine kinase receptors on the cell membrane of insulin-dependant tissues.
This increases glucose uptake by these tissues.
Which glucose transporters are insulin specific?
GLUT-4
Describe how insulin enables the uptake of glucose by adipose and muscle.
Insulin stimulates the mobilisation of GLUT4 transporters so they can move from the cytoplasm to the membrane.
Now glucose can be transported into the cell.
Most tissues do not require insulin to take up glucose. Which two tissues require insulin to uptake glucose?
Muscle
Adipose (fat) tissue
GLUT-4 is the only insulin dependant glucose transporter. The others do not.
Where would you find GLUT-1 and GLUT-3 transporters?
Brain, kidney and RBC’s
GLUT-4 is the only insulin dependant glucose transporter. The others do not.
Where would you find GLUT-2 transporters?
Beta cells of the pancreas and liver
Why does the liver require insulin for glucose uptake if the liver is not an insulin-dependant tissue?
The liver gets glucose by GLUT-2 transporters which are insulin dependant
As well as lowering BG, insulin increases glycogen synthesis in the muscle and liver. How?
Stimulated glycogen synthase and inhibits glycogen phosphorylase.
List the additional actions of insulin as well as it’s primary role of lowering BG.
-Increases glycogen synthesis in muscle and liver AND inhibits glycogen phosphorylase.
-Increases amino acid uptake into muscle which promotes protein synthesis.
-Increases protein synthesis AND inhibits proteolysis
-Increases triacylglycerol synthesis AND inhibits lipolysis
-Inhibits enzymes of gluconeogenesis in the liver
-Has permissive effect on growth hormone
->I wouldn’t necessarily worry about remembering all the details, just read through and be aware of how insulin has additional roles in stimulating and inhibiting certain processes
Glucagon increases insulin release too. This seems strange, but why does this occur?
Insulin is required to take up the glucose that is created via gluconeogenesis promoted by glucagon.
Otherwise, the glucose in blood would not be accessible to cells, muscle and adipose tissue.
List some other GI related hormones which can increase the release of insulin.
Gastrin
Secretin
CCK
->these act as a warning to the pancreas to say there’s a lot of glucose coming and currently being digested so the pancreas starts to secrete insulin ready
Which nerve activity also increases insulin release?
Vagus nerve
-> key nerve in controlling GI function and is similar to the hormones mentioned previously so pancreas knows there is a lot of glucose coming after digestion
List some stimuli which inhibit the release of insulin.
Low BG levels
Somatostatin
Sympathetic alpha 2 mediated effects
Stress e.g. hypoxia
If giving insulin, would you get a greater increase if administrating it orally or via IV?
Why?
Orally
-> there would be increased insulin by direct effect of increase glucose on beta cells. This is the same if given I.V.
However, if given orally, there is also vagal stimulation of B cells which will release incretin hormones (hormones which stimulate insulin secretion)
Just read through:)
Is glucagon an anabolic or catabolic hormone?
Catabolic
Which type of hormone is glucagon?
Peptide hormone
Which cells produce glucagon?
Alpha cells of pancreatic islet cells
Where does glucagon mainly act upon?
The liver
Which hormones are involved in the glucose counter-regulatory control system?
Glucagon
Epinephrine
Cortisol
Growth hormone
In which state of the body is glucagon most active?
Post-absorptive state
What are the insulin receptors?
Tyrosine-kinase linked receptors
What are the glucagon receptors?
G-protein coupled receptors
The glucagon receptors, G-protein coupled receptors are linked to the adenylate cyclase/cAMP system,
When activated, phosphorylate specific liver enzymes. This results in which processes?
- Increased glycogenolysis (breakdown of glycogen)
- Increased gluconeogenesis (formation of glucose)
- Formation of ketones from fatty acids- lipolysis
What is the storage form of glucose?
Glycogen
Where can glucose be stored in the form of glycogen?
Muscle or liver
What happens in glycogenolysis?
Glucagon stimulates the conversion of liver glycogen into free glucose
The brain uses glucose for energy. However, what can it use if necessary?
Ketone bodies
How can ketone bodies be produced?
Via beta-oxidation of free fatty acids
What happens in terms of insulin and glucagon when there is an increase in glucose?
Increase in insulin
Decrease in glucagon
What happens in terms of insulin and glucagon when there is an decrease in glucose?
Increase in glucagon
Decrease in insulin
What is secreted when amino acids are in the plasma?
Both insulin and glucagon.
Describe what would happen if we ate a meal high in protein with very little carbs.
Increased amino acids in plasma.
Insulin stimulated to uptake amino acid.
Decrease in blood glucose.
Counteracted by simultaneous release of glucagon to maintain blood glucose levels.
The brain gets priority over glucose for energy.
What can most other tissues use instead for energy?
Free fatty acids
Ketones
List some stimuli which promote glucagon release.
-Low BG
-High amino acid level in plasma
-Sympathetic innervation and epinephrine
-Cortisol
-Stress e.g. exercise, infection
Lit some of the stimuli which inhibit the release of glucagon.
-Glucose
-Free fatty acids and ketones
-Insulin
-Somatostatin
What happens to insulin level when there is an increase in parasympathetic activity?
Increase in insulin
->anticipation of digestion
What happens when there is an increase in sympathetic activity?
Promotes glucose mobilisation therefore increase in glucagon and epinephrine. There will be inhibition of insulin.
Name the four hormones which help to increase blood glucose.
Glucagon
Epinephrine
Cortisol
Growth hormone
->the fact there are four really highlights the importance of maintaining blood glucose levels for brain function
Which hormone antagonises the action of insulin?
Growth hormone
The four hormones which help to raise blood glucose levels are known as the counter regulatory hormones.
What do these hormones promote?
The formation of new glucose (gluconeogenesis) and break down of fatty adipose tissue (lipolysis)
Which processes does glucagon stimulate?
Liver glycogenolysis
Gluconeogenesis
Lipolysis
Which processes does epinephrine stimulate?
Muscle glycogenolysis
Liver glycogenolysis
Gluconeogenesis
Lipolysis
Which processes does cortisol stimulate?
Gluconeogenesis
Inhibition of glucose uptake
Lipolysis
Protein catabolism
Which processes does growth hormone stimulate?
Gluconeogenesis
Inhibition of glucose uptake
Lipolysis
High levels of cortisol can lead to which disease?
Cushing’s disease
Which type of hormone is somatostatin?
Peptide hormone
Which cells secrete somatostatin?
D cells of the pancreas
What is the main function of pancreatic somatostatin?
Inhibit activity of the GIT
Which condition can be helped by using synthetic somatostatin?
Life threating diahorrea
->this is because it slows gastric motility
What does somatostatin suppress the release of?
Insulin and glucagon
Patients with somatostatin releasing tumours will develop symptoms of which condition?
Diabetes
->this is because it supresses the release of insulin and glucagon
In those with somatostatin secreting tumours, how do you get rid of the diabetes symptoms?
Removing the tumour
Why does blood glucose increase in those with somatostatin secretin tumours despite the fact that the release of insulin AND glucagon is prevented?
Insulin is the only hormone which can reduce blood glucose.
However, glucagon is only 1/4 which can raise levels hence why levels continue to rise and give diabetic symptoms
Somatostatin released from the pancreas is identical to which hormone?
Growth inhibiting hormone released from the hypothalamus which can also be known as somatostatin
Can insulin inhibit the release of glucagon?
Yes
Can glucagon inhibit the release of insulin?
No- it stimulates it as the body needs to be able to take the glucose up
