Acute Regulation of Glucose Flashcards
What is normal plasma glucose concentration?
Between 3 and 10 mM
What is plasma glucose concentration after eating and between meals?
Portal vein glucose conc can reach 20 mM after eating
Between meals it could decline to 0 mM without replenishment
What are the passive transporters of glucose?
What is their role?
GLUT
They transport glucose out of the cells and into the circulation, down a concentration gradient
What is the role of Na+ symporters for glucose transport?
SGLT-1 and SGLT-2
These are secondary active transporters that take up glucose from the gut lumen into cells
Where is GLUT-1 found and why?
Brain and red blood cells
There always needs to be some uptake of glucose as the brain and RBCs only use glucose
What passive porters are involved in regulating blood glucose level?
The balance between GLUT-4 and GLUT-2
What happens to GLUT-4 when insulin levels are high?
More GLUT-4 passive porters are placed into the membrane, allowing cells to take up more glucose
Where is GLUT-4 found?
How would it be described?
skeletal muscle, heart, adipocytes
It is insulin-responsive
What is significant about GLUT-5?
It is a fructose transporter
What are the types of cells in the islets of Langerhans and what do they secrete?
Alpha cells secrete glucagon
Beta cells secrete insulin
The beta cells are in the middle of the gland, and the alpha cells are scattered around the outside
What other cells are found in the islets of Langerhans?
delta cells that secrete somatostatin
F cells that produce pancreatic polypeptide
How are cells in the islets of Langerhans distributed?
beta cells are mainly central and most abundant
alpha cells are at the periphery
the blood will pick up insulin, followed by glucagon, before passing into the circulation
What do beta cells sense?
They sense glucose (and amino acids) in the blood, by using it to make ATP
What is the role of the ATP-gated K+ channel in the membrane of the beta cell?
It closes when there is lots of ATP present (produced from glucose)
The cell depolarises
What happens when the K+ channels on the B cells shut?
Depolarisation triggers voltage-gated Ca2+ to open, leading to calcium influx
This leads to secretion of insulin by exocytosis
What is the role of GLUT-2 transporters in beta cells?
As glucose conc starts to rise, the GLUT-2 transports more glucose into the cell
They are insulin-insensitive and low-affinity
What is the difference between insulin concentrations after oral and IV glucose is given?
There is a rapid and large increase in insulin production after oral glucose is taken
If there is a slow IV infusion of glucose, there is a much smaller rise in insulin concentration
Why does insulin concentration rise higher when oral glucose is taken?
There are other aspects to eating that enhance the insulin response
How do CCK and parasympathetic input influence insulin release?
ACh (parasympatheti NS) and CCK are activated once a meal has been eaten
They signal through Ca2+ cascade to enhance insulin release
What are incretins?
a group of metabolic hormones that stimulate a decrease in blood glucose level
What is the role of an incretin?
They will act via cAMP or PLC pathways to increase exocytosis of insulin
How does the autonomic nervous system influence insulin secretion?
The PNS will drive insulin secretion
The SNS will inhibit insulin secretion
How does action of a-adrenergic agonists affect insulin release?
This involves sympathetic stimulation
This suppresses insulin release
Where is insulin produced?
What type of hormone is it initially?
It is a preprohormone produces in the ER
It is one long chain containing lots of cysteine residues that cross-link by disulphide bonds
What forms the folded structure of insulin after it is cleaved?
It is cleaved to a prohormone which is folded up by internal disulphide bonds
What happens to insulin during processing in the Golgi and secretory granules?
It is cleaved to give A and B chains (held together by disulphide links) and a free C peptide
What is the role of C peptide?
It is inactive
It is used clinically as a marker of endogenous insulin production
(how much insulin the patient is producing)
What type of receptor is the insulin receptor?
It is a receptor tyrosine kinase
The receptor dimerises through disulphide bonds