Pancreas & insulin Flashcards
Aantomy of pancreas & how it develoops!
Largest Gland in body!
develops embryologically as an outgrowth of the foregut
Describe the contents and structure of the pancreas
& functions of the pancreas
2 functions:
• ~ 1% endocrine tissue, 99% exocrine tissue
Exocrine: (acinar cells)
- produces digestive enzymes secreted directly into duodenum which forms the bulk of the gland
- Alkaline secretions through pancreatic duct into the duodenum
Endocrine: (Islets of Langerhans)
- hormone production
Describe what each endocrine cell of the pancreas secretes.
Delta “dogs”>> dont care about aplha or beta.. they inhibit humans in general (universal inhbitor of hormones) ;P
- Beta (β)-cells >> insulin
- Alpha (α)-cells >> Glucagon
- Delta (d)-cells >> somatostatin
- PP (pancreatic polypeptide) cells>> PP
- e cells>> Ghrelin
- G cells >> gastrin
- VIP (vasoactive intestinal peptide)
what do beta cells secrete?
• Major cell types in islets of langerhans?
How many disulphide bonds are present in a molecule of the hormone insulin?
3
Insulin structure (prcoess)
THe signal part “Pre” = ensures thes newly synthesizd protein enters the costernsl space of the ER
C-chain= connecting chain
insuling strucutre
(final)
polypeptide (A and B chains) interlinked by disulfide bonds!
- (additional intra-chain disulfide bond w/in the A chain)*
- Insulin is a big peptide with an alpha helix structure*
Synthesis of insulin (in the cell) and importance of C peptide
signal peptide is removed once it enter the ER, the remained prp-insulin folds and disulfide bonds form btw Cystine residues.
pro-insulin > Golgi & C-chain is cleaved off!
the final storage vesciles have equal amount of Cpeptides to insulin.
this makes the C peptide a good marker for measuring endogenous insulin release!
how is insulin stored?
it is stored in the B-cell storage granules as crystalline- ZINC insulin molecules!
how is insulin secreted?
glucose comes and attaches to GLUT 2 , it flips and glucose is released inside the cell (against its concentration gradient),
Glucose is converted to G-6-P by Glucokinase!, the phosphate group is so charged that it cannot pass through the membrane >> Glucose is now trapped!
More ATP produced from the metabolism of glucose results in inhibition of the ATP-sesnsitve potassium channels (KATP channels). >>Less positively charged potassium leaving the cell through K+ ATP channels results in depolarisation of the plasma membrane (i.e. makes the resting membrane potential less negative).
This depolarisation is sensed by voltage activated Ca+ channels which open allowing calcium to flow down its electrochemical gradient into the cell.
It is this influx of calcium ions into the β cell that activates the insulin containing vesicles causing them to fuse with the plasma membrane and release insulin.
what controls insulin secretion?
what stimulates its secretion?
what inhibits it?
actions of insulin
(favours storage)
1/2 life of insulin?
5 mins there is no carrier (cuz theyre water soluble)
insulin recepter strucutre!
tyrosine kinase
which cells have GLUT 2 transporters?
describe the K-atp cahnnels and their role in secreting insulin.
when ATP-K+ channels r closed>> no K+ leaves>> membranes become depolarised >>(-50mv)
another thing occurs….
Ca+ channels sense the change in voltage and the sensitive Ca+ channels open! and ca+ comes in! (bc ca is higher outside remeber?)
they’ll go and stimulate the vescies and release insulin bara!!
if someone is glucokinase deficient, what happens?
they cannot secrete the insulin effectively!
this will lead to diabetes mellitus type 2 due to dysfunction of glucokinase!>> insulin isnt secreted from B cell!
**********
but this type of diabetes occurs in young ppl!
(remember type 2 ususlaly occurs in elderly)
MODY
(Maturitiy onset diabetes melliutis of young ppl)
which drugs can inhibit the Atp -voltage gated K+ channels? why r they used
sulphonyl Ureas!
tolbutamiode
glycomide!
Meglitinides!
to treat diabetes type 2, blocks K+ channels > memebrane is more easily depolarized, more Ca2+ comes in>> more insulin released!….YAAAAY
what r the natural antidiabetic hormones?
Incretins!
what r the main target tissues for insulin?
-liver, skeletal msucle and adipose tissue!
normal glucose amounts in body?
after a meal?
renal threshold?
Normally 3.3-6 mmol/L
After a meal 7-8 mmol/L
Renal threshold 10 mmol/L
- Pregnancy renal threshold↓
- Elderly renal threshold↑
As C-peptide is released with insulin in equimolar amounts, i
ts level in plasma is a useful marker of endogenous insulin release.
Measurement of plasma C-peptide levels in patients receiving insulin can be used to monitor any endogenous insulin secretion.
structure of Glucagon? secreted by what cells?
actions?
Alpha cells
opposite of INSULIN!
No disulphide bridges: =flexible structure
The major actions of glucagon are:
- Increase glycogenolysis and decrease glycogenesis in liver.
- Increase gluconeogenesis in liver.
- Increase ketogenesis in liver.
- Increase lipolysis in adipose tissue.
what triggers GLucagon release?]
what inhibits it?
triggered>> a decrease in blood Glucose concentration!
inhibited>> by insulin and an increase in Blood glucose concentration
Mechanism of action of GLucagon (which recepter type)?
G-protein coupled recepter
Diagnosis of Diabetes mellitus
Diagnosis basis of venous plasma glucose concentration:
normal range 3.3-6mmol/L plasma glucose
fasting ≥ 7.0mM
random ≥ 11.1mM
just review
Which term is used to describe the excretion of glucose in urine?
Glucosuria (sometimes called glycosuria)
which GLUT transporter is in the brain?
GLUT 3
