the endocrine pancreas Flashcards
what occurs in type 1 diabetes to lead to insufficient insulin production?
-autoimmune destruction of beta cells
what occurs in type 2 diabetes to lead to insufficient insulin production?
-insulin resistance and beta cell dysfunction
what are some risk factors for T2DM?
- family history
- obesity
- pregnancy
- calorie dense diet
- sedentary lifestyle
- paternal and maternal metabolic health
what are islets?
-clusters of about 1,000 endocrine cells
what cells make up the pancreas?
- islets make up 1 to 2%
- remainder are mostly exocrine pancreas (which secretes digestive enzymes)
what do alpha cells islets secrete?
glucagon
what do beta cells islets secrete?
insulin
what do delta cells islets secrete?
somatostatin
what do PP cells islets secrete?
pancreatic polypeptide (PP)
what do E cells islets secrete?
ghrelin
what colours are insulin, glucagon and somatostatin under immunoflourence?
insulin=red
glucagon=green
somatostatin- blue
what islets are most abundant?
Beta cells
what glucose state do we want our body to be in?
normaglycaemia
right after fasting/exercise (before hormones have an effect) what glucose state will the body normally be in?
hypoglycaemia
right after feeding (before hormones have an effect) what glucose state will the body normally be in?
hyperglycaemia
how is mature insulin synthesised from the nucleus of a pancreatic beta cell?
- mRNA is translated in the rough ER forming pre proinsulin
- pre proinsulin is transferred to the golgi apparatus where disulfide bridges are made between the alpha and beta chain forming proinsulin
- pro insulin is then cleaved into insulin and C peptide which are released into the plasma
what intracellular mechanisms occur for producing insulin from when glucose enters the cell?
- glucose enters the cell by diffusion through GLUT 1/2
- glucose is then phosphorylated to glucokinase which can then be used in glycolysis
- glycolysis produces ATP which blocks the KATP channel
- this causes depolarisation and triggers the opening of the voltage gates Ca2+ channels
- influx of calcium triggers insulin vesicles to bind to pancreatic beta islet cell and secretion of insulin
how would you describe the way (trend?pattern?) in which insulin is secreted?
biphasic
1st phase= big, quick spike in insulin to try stop hyperglycaemia
2nd phase= more controlled and usually more suited to what the person needs, this is usually a lower spike and longer
what is an early marker for pre diabetes in terms of the phases of insulin release?
an early marker is the 1st phase is decreased first
what occurs to the phases of insulin release in type 2 diabetes?
-normally both are decreased
beta cells are still there when they are desensitized due to type 2 DM
True or False
True- they have just degranulated or dedifferentiated so no longer function
what is the intracellular process that causes glucagon to be released in alpha cells?
- glucose levels drop
- glucose enters alpha cell through GLUT transporter
- glucose metabolism is low meaning there’s low levels of ATP
- due to low ATP KATP channel open only partially allowing potassium to leave the cell
- Voltage gated sodium channel allows sodium to enter the cell
- potassium leaving the cell and sodium entering the cell causes a change in the alpha cell membranes action potential
- change in action potential allows voltage gated calcium channel to open, letting calcium flow into the cell
- increase of calcium in the cell causes glucagon exocytosis
what is the intracellular process in alpha cells to stop glucagon from getting released when there is high glucose levels in the blood?
- glucose enters through GLUT transporters
- glucose metabolism is high which causes lots of ATP to be produced
- ATP blocks the KATP channel, stopping potassium from leaving the cell
- blocking of KATP channel means theres not a change in membrane potential so the voltage gated sodium channel cant open
- due to glucose being greater the SGLT2 glucose transporters bring sodium ions into the cell in a non voltage manner (by diffusion)
- due to no change in action potential the calcium voltage channels remain shut meaning that calcium cannot flow in to the cell and glucagon can not be released
what is gluconeogenesis?
formation of glucose from noncarbohydrate precursors such as lactate, amino acids and glycerol
what is the relation between how much glucagon alpha cells secrete and blood glucose?
alpha cells secrete glucagon inversely proportional to blood glucose
what organ does glucagon act on?
liver
what effect foes somatostatin 14 (sst14) have on beta and alpha cell function?
it suppresses beta and alpha cell function