Postprandial Glucose Metabolism - Pancreatic Function Flashcards
(30 cards)
How many cells are in each islet of langerhans?
50-300
What are the four types of cells in the islets of langerhans?
alpha, beta, delta and theta
What hormone do beta cells secrete?
insulin and amylin
What hormone do alpha cells secrete?
glucagon
What hormone do delta cells secrete?
somatostatin
What hormone do theta cells secrete?
pancreatic polypeptide
Which hormones cleave insulin?
prohormone convertase 1 and 2
Which part of the proinsulin molecule is cleaved to make insulin?
the c peptide
How are the two peptides of insulin connected?
disulphide bonds
Where is preproinsulin converted to proinsulin?
in the microvesicles after the rough endoplasmic reticulum
Where is proinsulin converted to insulin?
in the vesicles after the golgi apparatus
What are the two phases of insulin secretion?
1st phase is a sharp rise in insulin that lasts for 2-5 minutes and the 2nd phase is a prolonged secretion that lasts for the duration of the stimulus
Describe the cellular events in glucose induced insulin secretion
glucose enters the cell via GLUT-2 transporter, glucose is converted to G-6-P by glucokinase, glucose goes through glycolysis and the krebs cycle to produce ATP, the increase in ATP closes the potassium channel which depolarises the membrane which opens the voltage gated calcium channel, the entry of calcium into the cell allows the release of insulin from vesicles
What is the Km of GLUT-2 and glucokinase?
high Km so that the process is not easily saturated
What other nutrients can induce insulin secretion other than glucose?
amino acids and fatty acids
How do amino acids induce insulin secretion?
by increasing ATP in the cell in the same way that glucose does
How do fatty acids induce insulin secretion?
the fatty acids have to be converted to malonyl CoA
Why is more insulin secreted when glucose is ingested orally rather than intravenously?
because incretins (gut derived hormones) which are produced in response to nutrients in the gut also stimulate insulin secretion
What are the two main incretins and where are they secreted?
GIP from the K cells in the upper small bowel and GLP-1 from L cells in the lower small bowel
What are the actions of GLP-1?
inhibits glucagon secretion, stimulates insulin synthesis, promotes beta cell proliferation, promotes beta cell differentiation, stimulates beta cell maturation, inhibits gastric emptying
Why dont incretin based therapies cause hypoglycaemia?
because incretins dont release insulin if blood glucose isnt high
What incretin based therapies are available for diabetes treatment?
DPP-4 inhibitors which inhibit the enzyme which destroys GLP-1 and GLP-1R agonists
What are liraglutide and exenatide?
GLP-1R agonists
What is bydureon?
a long acting GLP-1R agonist
