Insulin Secretion and Action Flashcards
On which chromosome is insulin coded for? Where is it synthesised?
Chromosome II // Rough ER of pancreatic beta cells
What type of hormone is insulin? It is actually synthesised as what?
Peptide hormone // Synthesised as a larger preprohormone- preproinsulin
What is an important byproduct of the cleavage of preproinsulin to insulin? What is its function?
C-protein // No physiological function but is a good marker of insulin production
Glucose enters the pancreatic beta cell via what transporter? In association with which enzyme?
GLUT2 // Glucokinase
What is the function of glucokinase?
Glucose –> Glucose-6-phosphate
Metabolism of glucose in the beta cell generates ATP. What does this cause within the cell?
Closure of K+ channels in the cell membrane
What does closure of the K+ channels in the cell membrane of the beta cell cause?
Depolarisation, which results in opening of Ca++ channels and entrance of Ca++ into the cell
The entrance of Ca++ into the pancreatic beta cell has what action?
Exocytosis of insulin from the granules
After secretion, where does the insulin enter? Where is it carried to?
Portal circulation // Liver
C peptide is mainly broken down by which organ?
Kidneys
Blood glucose is closely regulated and rarely strays outwit what range?
3.5-8mmol/L
What is the principle organ of glucose homeostasis?
Liver
What are the roles of the liver in glucose homeostasis?
Absorbs and stores glucose as glycogen // Releases glucose into the circulation between meals to match glucose utilisation // Forms glucose via gluconeogenesis if really needed
What is broken down to form glucose in gluconeogenesis?
Fat, muscle and protein
What organ is the major consumer of glucose? Its function depends on what?
The brain // Relies on uninterrupted supply of glucose
Glucose uptake by the brain has what relationship with insulin?
It is not insulin dependent
Tissues such as muscle and fat have insulin responsive glucose transporters and absorb glucose in response to what?
Post-prandial peaks in glucose and insulin
What happens to glucose taken up by muscles?
Stored as glycogen or metabolised to either lactate or CO2 and H2O
Fat uses glucose as a substrate for what?
Triglyceride synthesis
What products are released from lipolysis?
Fatty acids and glycerol
What is the action of insulin in the fasting state?
Regulation of glucose release by the liver
What is the action of insulin in the post-prandial state?
Promotes glucose uptake by fat and muscle
What hormones counteract insulin?
Glucagon, adrenaline, cortisol, GH
Are cell membranes permeable to glucose?
Not inherently
What are used to carry glucose through the cell membrane and into cells?
GLUT transporter proteins
Which transporter enables basal, non-insulin stimulated glucose uptake into many cells?
GLUT1
What is the function of GLUT2?
Transports glucose into the pancreatic beta cell
Which transporter enables non-insulin dependent mediated glucose uptake into brain neurones and the placenta?
GLUT3
What is the function of GLUT4?
Transports glucose into muscle and adipose tissue cells following stimulation of the insulin receptor
What subunits does the insulin receptor involve? Which includes the insulin binding site?
2 alpha and 2 beta // Alpha
When insulin binds to the alpha subunit of its receptor, what happens?
There is a conformational change in the beta subunit, activation of tyrosine kinase and an intracellular cascade
The intracellular cascade which occurs after insulin has bound to its receptor results in what?
Transport of the GLUT4 transporter to the cell surface and hence increased transport of glucose into the cell
