BIOC Lecture 2: Insulin Flashcards
What is the key metabolic pathways active in the goldfish when it is producing ethanol?
Glycolysis
What is the difference between humans and goldfish’s metabolic rate?
Goldfish have a very reduced metabolic rate, therefore function less efficiently
Without oxygen, what do goldfish convert lactate to?
Ethanol
What is insulin synthesised as?
A pre-pro-peptide
What is a pre-sequence?
A signal that helps tell the cell where this protein is going to go in the cell
What is the specific pre-sequence for insulin synthesis?
Responsible for export from the cytosol of the cell into secretory granules
What is pro-sequence?
segment of a protein that assists in folding, stabilization, regulation of activity, ensuring the protein is only active under appropriate conditions and at the correct location
What is the pro-sequence of insulin important for?
For proper folding of insulin and is then removed
Mature insulin has how many chains of amino acids?
2 chains of AA’s - with cleavages
Insulin will only function when?
the 2 components are properly folded and connected
What type of bonds does insulin have?
disulfide bonds (C-C) as well as secondary and tertiary structure interactions
Where are alpha and beta cells made?
Pancreas
What do beta cells cause the release of?
Insulin
What does insulin lead to?
Decrease in blood sugar
What do alpha cells cause the release of?
Glucagon
What does glucagon lead to?
Increased blood sugar
What does insulin typically form?
Hexamers with Zn in beta cells
What does insulin form in the blood?
Monomers
What does circulating insulin interact with?
Receptors on some tissues (fat, muscle, liver etc)
What is an insulin receptor synthesised as?
One protein - cleaved for full function
What gives rise to different receptor isoforms?
Splicing variants during mRNA
Where are insulin receptors found?
As a dimer on the surface of various cell types
What is a dimer?
when two similar molecules or proteins link up together
What three domains play a specific role in the insulin receptors function?
Extracellular, transmembrane, cytosolic
What happens when no ligand is present?
The receptor is inactive
What does binding of ligand do to receptors?
Causes structural changes and activates receptor (tyrosine kinase domain)
What happens in a normal person when blood glucose levels rise?
- Insulin is released by beta cells
- Receptor stimulated, GLUT4 receptors move to cell surface
- Glucose uptake
What is happening in the body of people with Type 1 diabetes?
No functional insulin: autoimmune disease or variant insulin
What is happening in the body of people with Type 2 diabetes?
Reduced receptor sensitivity: obesity (common) or rare genetic receptor variants
What are beta cells sensitive to?
Insulin sensitive
What does the uptake of glucose stimulate?
Oxidative metabolism and production of ATP
What does increased metabolic activity stimulate?
The conversion of proinsulin and the release of insulin
What do storage granules fuse with?
With membrane and are released into the bloodstream
How many glucose transporters are know in humans?
As many as 20
How many main transporters are there?
4
What are the 4 main glucose transporters?
GLUT 1, 2, 3, 4
What is the function of GLUT 1?
Bidirectional and found in foetal tissues. In adults, found in erythrocytes and in low levels in most cells where it allows basal uptake of glucose for respiration
Where is GLUT 2 found?
In kidney, liver, pancreatic B cells, basolateral membrane of small intestine
What is the function of GLUT 2?
Largely responsible for the insulin-independent uptake of glucose, and for release of glucose during periods of gluconeogenesis.
What is the function of GLUT 3?
Glucose uptake in neurones and also in the placenta
What is the function of GLUT 4?
Insulin-dependent glucose uptake
Where is GLUT 4 found?
In striated muscle and adipose tissue
Where does GLUT 4 transition between?
Vesicles within the cell and plasma membrane
What are the processes of GLUT4 activation?
Endo- and exocystosis
What does insulin favour?
GLUT4 location in plasma membrane
