Pancreatic Function Flashcards
Which tissue secretes incretins?
The gut - mainly small intestine
Which peritoneal compartment is the pancreas in?
Retroperitoneal
Why does bydureon (long lasting exenatide) cause greater weight cf to exenatide?
The addition of a FA to increase HL means it can cross the BBB and suppress apeptite to a greater degree
Is glucose the only nutrient to stimulate insulin secretion?
No, aa’s and FAs also do
Why can’t you use GLP-1 for T1DM?
No beta cells for it to act on
What type of molecule is exenatide?
GLP-1R agonist - a lizard GLP-1 equivalent with a much longer half life than human GLP-1
How is amylin being used therapeutically?
Incombination with pramlintide for weight loss
What is the structure of the insulin protein?
Two peptide chains
Why is more insulin released in response to oral glucose cf to IV glucose?
The incretin effect
What is mechanism of action of DDP-4 inhibitors?
Inhibitors DDP-4 (which degrades incretins) to increase the effect of endogenous incretins
What is the effect of GLP-1?
Increase synthesis of proinsulin in response to high glucose (not normal glucose)
Inhibits glucagon release
Promotes Beta cell proliferation, maturation and differentiation
What are the two stages of insulin secretion?
- Rapid, within 2-5 minutes, exocytosis of vesicles close to the surface
- Prolonged duration secretion phase, lasts for the duration of stimulation
What is a possible drawback to GLP-1 therapy?
Pancreatitis
Pancreatic cancer
What is the main side effect of exenatide?
Nausea
What are the cells of the Islets of Langerhan?
Alpha
Beta
Delta
Phi
How is insulin stored?
In secretory granules
In which aspect of the Islet of Langerhan are beta cells located?
The core
What is the effect of amylin?
Inhibit glucagon secretion
Delays gastric emptying
Inhibits food intake
Explain the mechanism of insulin secretion in response to glucose?
- Glucose enters via GLUT 2 receptors
- It is phosphorylated by glucokinase into G6P
- This enters the TCA cycle
- The ratio of ATP/ADP increase
- This blocks K efflux channels
- The membrane potential of the cell changes
- Ca influx through voltage gated channel
- Insulin is released from secretory vesicles
Which tissues have glucokinase?
Beta cells
Liver
What happens to insulin secretion over the course of progressive T2DM?
Secretion decreases
Which Islet of Langerhan cells produces somatostatin?
Delta
Which cells release amylin?
Beta-cells
What are the names of the incretins of note?
Glucagon like peptide 1 (GLP-1)
Glucose induced insulinotrophic polypeptide (GIP)
