The endocrine pancreas Flashcards
Give a summary of the glucostatic theory
Our drive to eat is driven by our glucose levels
Give a summary of lipostatic theory
Our drive to eat is driven by fat stores
What is the function of leptin
Peptide hormone driven by fat stores which depresses feeding activity through its affect on the hypothalamus
What are the 3 categories of energy output
cellular work - transporting molecules across membranes, growth and repair, storage of energy
mechanical work - movement using muscle
heat loss - associated with cellular and mechanical work
what are Anabolic pathways
Building up of larger molecules from smaller ones
(remember anabolic steroids - build up muscle therefore anabolic pathways build up bigger molecules)
What are catabolic pathways
Degradation of large molecules into smaller ones which releases energy
What is an absorptive state
Ingested nutrients supply the energy the body needs and the the excess is stored (anabolic phase)
When does an absorptive state occur
After eating
What is a post absorptive state
(fasting state)
Rely on body stores to provide energy (catabolic phase)
When does a post absorptive state occur
Between meals and overnight
What does it mean to be an obligatory glucose utiliser and give an example
It can only use glucose for energy for example the brain
What is the normal range of blood glucose
3.2-6.3 mM
What organ has first access to glucose in the blood
The brain
What is excess glucose converted into
fat stores or glycogen
What is glucagon
Catabolic hormone which breaks down glycogen stores and activates enzymes to break down amino acids into glucose
What is insulin
Anabolic hormone which stimulates production of fat and glycogen from glucose
Why is glucose excreted in the urine in diabetics
They don’t have enough insulin to deal with increased blood glucose levels so when the blood gets to the glomerulus, the kidneys have too much glucose to deal with so the excess gets excreted
What organ releases insulin and glucagon
pancreas
How much of the pancreas has endocrine function and where in the pancreas are insulin and glucagon produced
1% is endocrine and insulin and glucagon are produced in the islets of langerhans
What do alpha cells of the islets of langerhans produce
glucagon
What do the beta cells of the islets of langerhans produce
insulin
What do the delta cells of the islets of langerhans produce
Somatostatin
When is glucagon released into the plasma
When the blood glucose levels decrease
When is insulin released into the plasma which causes glucose to be up taken into cells to decrease plasma blood glucose
When the blood glucose in the plasma is very high
And when amino acids enter the blood from the GI tract
Describe how insulin is synthesised
It is synthesised as a large preprohormone - preproinsulin which is then converted into proinsulin
Proinsulin is then packaged into secretory Vesicles which has enzymes which cleave the proinsulin into insulin and C peptide insulin
Why os C peptide a good marker for pancreatic health
it resists degradation and persists in the plasma, longer than insulin
Which hormone dominates the absorptive state
Insulin (anabolic)
What is glucose stored as in liver and muscle
Glycogen
What is glucose stored as in liver and adipose tissue
Triacylglycerols
What causes beta cells to release insulin
They have a special Katp channel which is sensitive to ATP
When glucose is abundant, it enters cells through the GLUT transported and metabolism increases which causes more ATP to be produced in the cell which causes the channel to close. Intracellular potassium then rises which depolarises the cell which causes voltage gated calcium channels to open and triggers insulin to be exycytosed from their vesicles to be released into the circulation
What is the primary action of insulin
Binds to tyrosine kinase receptors on the cell membrane of insulin dependent tissues to increase the glucose uptake in that cell
How does insulin increase glucose uptake in cells
Mobilisation of GLUT-4 which is normally in the cytoplasm but migrates to the membrane which allows more glucose to be up taken into the cell
What are the insulin dependent cell types
Muscle and fat
What GLUT transporter is insulin dependant
GLUT-4
What transporter does the liver use for glucose uptake
GLUT 2 which is insulin independent
How does insulin indirectly alter glucose transport in hepatocytes
It breaks down glucose into glucose-6-phosphate which keeps the glucose concentration in the hepatocyte low which maintains the gradient for more glucose to enter the cell
What is the effect of insulin on glycogen synthesis in muscle and liver
Stimulates glycogen synthesis and inhibits glycogen phosphorylase
What is the effect of insulin on amino acid uptake
Increases it which promotes protein synthesis
What is the effect of insulin on triaglycerol synthesis
Increases it in adipocytes and liver by stimulating lipogenesis
What is the effect of insulin on gluconeogenesis in the liver
inhibits it
What is the relation between insulin and growth hormone
Permissive effect - insulin is required for Growth hormone to be active and working
What is the effect of insulin on potassium entry
Stimulates sodium potassium ATPase so increases potassium entry into the cell
What happens to insulin receptors after the effects of insulin are completed
The receptors are endocytosed and destroyed by insulin protease
Why does glucose given orally cause bigger release of insulin then IV glucose
Because the release of GI hormones causes release of insulin as well as blood glucose and in IV glucose these hormones will not be released
What is the effect of vagal activity on insulin release
Increased vagal activity causes insulin release
What is the main target organ for glucagon
Liver
What are the hormones which are part of the glucose counter-regulatory system
Epinephrine, cortisol, growth hormone and glucagon
What does glucagon cause
Increased glycogenolysis
Increased gluconeogenesis
Formation of ketones from fatty acids
What does the brain use instead of glucose in severe cases of starvation
Ketones
What are potent stimulus for glucagon secretion
Amino acids but they also increase insulin levels
What is the effect of somatostatin on insulin and glucose release
Somatostatin inhibits both glucagon and insulin release
Why do cushings patients appear diabetic
They have high cortisol which inhibits insulin
What is the main function of somatostatin
Inhibit the GI tract
What occurs if insulin and glucagon are both inhibited
Blood glucose rises as there are multiple hormones which increase blood glucose but only insulin reduces blood glucose
What is the effect of insulin on glucagon
Inhibits glucagon
What is the effect of glucagon on insulin
stimulates insulin release
What is the effect of exercise on blood glucose
Decreases blood glucose because it increases glucose entry into muscle cells even in absence of insulin which causes increase in GLUT-4 transporters
It also increases insulin sensitivity
What happens during starvation with regards to production of energy
Adipose tissue is broken down and fatty acids are released - these are readily used by most tissues to produce energy
What does the liver convert free fatty acids into during starvation
Ketone =bodies which can be used by muscle and brain
What is ketone body uptake dependant on
insulin
What happens in type one diabetes
Autoimmune destruction of the pancreatic beta cells of the islets of langerhans which compromises ability to produce insulin
What do type one patients have an absolute need for
Insulin - without it they become excessively wasted and develop ketoacidosis
How does ketoacidosis occur in type 1 diabetes
No insulin results in a starvation like state due to glucose not being up taken into cells
This results in adipose being broken down into fatty acids and the excess free fatty acids converted into ketone bodies
Ketone bodies rely on insulin for their up take so without the insulin they stay in the plasma and due to their acidity cause acidosis
How are ketones detected
In the urine and can smell acetone in the breath
What happens in type 2 diabetes
Peripheral tissues become insensitive to insulin
What is type 2 diabetes associated with
obesity - chronic levels of exposure of high insulin due to their high glucose diets - this eventually builds an insulin resistance
How is diabetes detected
Glucose tolerance test - patients ingest glucose after fasting blood glucose is measured - the blood glucose should return to normal fasting levels within an hour - anything over 2 hours is indicative of diabetes
