Endocrine Function of the Pancreas Flashcards
Explain the basic anatomy of the endocrine functioning pancrease
location of each cell type
physiological function of the cells
Islets of Langerhans
- compose approx. 2% of the pancreatic mass
- these islets contain three types of cells; alpha, beta and delta
- islet are innervated by the parasympatheic stimulation - ach triggers the release of these hormones from these three types of cells
Alpha Cells (on the periphery/mantle)= secrete glucagon
Beta (in the middle) = secrete insulin
Delta (scattered throughout the mantle) = secrete somatostain = inhibitor of both insulin and glucagon
F cells = secrete pancreatic polypeptide hormone
- the exact location, with alpha on the outside and beta on the inside allows of physiological function
if insulin is NOT secreted into the blood as it passes from midle to exterior— then that stimulates glucagon to be released
Explain the blood flow thorugh the pancreas
- blood enters the Core of the islet at through arterioles
- pass through the mantle and break into capillaries
- carry blood enriched in insulin through th emantle
- collect into venules and feed into the heptaic portal vein
- first pass of liver effect occurs (50% of insulin doesnt make it out to circulation)
so blood is
- first expose to beta (insulin releasing cells)
- then to the alpha cells (glucagon releasing)
if the blood entering is high in glucose = triggers release of insulin from the beta cells
if there is circulation insulin, glucagon release is inhibited (if there is no insulin, glucagon is secreted)
how is insulin, as a hormone, synthesized
role of C-peptide
insulin is synthesized as a preprohormone
- its synthesis is stimulated by the presence of glucose in elevated levels
At the Cellular Level
- the signal sequence is cleaved off within the ER lumen
- C-peptide is utalized form the proper folding of the insulin
- then the C peptide is cleaaved off & insulin is there
thus, only homemade, self-produced insulin has the C-protein aka a good lab test to order to see fi your pt. is making thier own insulin or not
Insulin is cleared by the liver (first pass with 50%) and the kdienys
C-peptide is NOT!! cleared by liver thus can be checked
How is carbohydrate metabolism regulated
2 main hormones & additonal ones
specifics about insulin compared to these
Hormones Involved
- insulin
- glucagon
others include.. (these are blood sugar raisers, trigger an increase in BG) counter-reg. hormones
- epi
- cortisol
- growth hormone
- thyroid hormones
Insulin
- the only hormone which can lower blood sugar - thus it is the main anabolic hormone of the body
How is glucose transported into the cells
what types of receptors are specifi to the role of carbohydrate regulation
glucose binds to the receptors on cells which triggers an ability for insulin realease
glucose is water soluable - therefore does not readily pass through the membrane on its own –> needs a channel!
- but it will pass through channel without ATP use as it is facilitated diffusion from high to low concentrations
The transporters which allow glucose to pass a membrane are called GLUT = glucose transporters
GLUT-1 & GLUT-3 = function as basal glucose transport’ located everywhere
GLUT-2 = pancreatic B cells have these, they are there to sample the glucose in teh blood to see if insulin is needed or not
GLUT-4 = transporters foudn on skeletal and adipose tissue, intracellularly and are the mediators of glucose transport that is insulin mediated
- glut-4 transporters respond directly to insulin stimuli (insulin triggers these transporters to uptake glucose into the skeltal muscle and adipose tissue)
how does glucose levels within a beta cell trigger the secretion of insulin
at 0 mg/glucose what happens
at 100 mg/glucose what happens
at 150 mg/glucose what happens
at 0mg/dl gluose
- there is not a need for insulin (end goald = no insulin secretion)
- the membrane of the cell will exisit hyperpolarized (-75)
- with low glucose levels, this triggers ATP gated K+ channels to open: triggered by the presence of ADP
- K+ LEAVES the cell
- maintains its negative potential away from threshold
- no insulin secreted
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as glucose concentrations increase, the GLUT-2 cells (sampling) will take in more glucose, triggers ATP to close the Efflux, triggers calcium to trigger insulin to be released from vesicles within teh ER
this glucose taken in, is metabolized and creates ATP
at 100 mg/dl glucose
- at 100mg this allows ATP (energy from glucose) to be made
- this ATP means a LACK of ADP = therefore the K+ channels do not open, the cells potential gets closer to threshold (at -55)
At 150 mg/dl glucose
- high glucose = hight ATP:ADP ration
- ATP will keep that ATP-K+ gate CLOSED
- this will keep K+ inside, depolarizing the membrane (+++)
- there are spikes of this depolarization - of which the spikes trigger the voltage gated Calcium channels
- these channels open (essentially, its “too postivie” in the cell)
- calcium rushes in and this triggers insulin to be secreted
- eventually, K+ voltage channels open and let K+ leaves and the membrane is restored
what are the two phases of insulin response to glucose
why is oral glucose more effective thatn IV glucose
phase 1 = a rapid release of insulin that is preformed in vesicles waiting for thier signal (immediate peak)
phase 2 = a relase of insulin as its made continuously in the cell, slwoly over time
Oral gluc > Iv
- because oral glucose stimualtes GIP: gastrin inhibitory peptide: which helps to further decrease glucose in the blood by increasing the insulin response better than the action from IV (GIP not activated)
what stimulates insulin secretion
what inhibits it
where does it go
Stimulators
- glucose
- amino acids, GI hormones , B-ad. agonists
- ach
inhibitors
- insulin
- somatostain
- 2-deoxyglucose
glucose regulates the response of insulin, yes/no & other agetns impact the quaintiy of insuli release
Pathway of insulin
- portal circulation
- 50% used there, 50% moves to circulation ssytemic
- to skeletal muscles, liver, and fat
- triggers the uptake of glucose into these cells (via GLUT-4)
- can be down-regualted or up regulated at these sites
Explain the Insulin Receptor
what does a bound insulin to receptor trigger in a cell
insulin receptor
- a tyrosine kinase receptor
- on the OUTSIDE of teh cell: because insulin is a water soluable peptied hormone (binds to the alpha receptors on the exterior of teh receptor)
- found majority on adipose tissue, skeletal muscle & brain (but brain relies on glut-1 & 3)
Triggers
- triggers a downstream cascadeof effects to created
- glucose uptake into the cell
- syntehsize glycogen from glucose for storage
- increase amino acid entry to cell
- allow K+ to enter
full effects of insulin are seen at lows levesl of receptor binding - at 25% of the receptors occupied is when the full activity is achieved
the action of insulin the liver is directly related to the amount of insulin that is bound
Direct Anabolic actions of insulin
Insulin takes simple molecules and builds them up to larger more complex structures
liver
- glucose is build up into chains of glyocen
Adipose
- glucose is taken up into the cells of adipose tissue
- and fatty acids are released as a resulyt of glucose uptkae
fatyy acids are then converted into ketones through the liver
muscles
- uptake of glucose inot muscle cells and amino acids are also taken up to build new tissue
describe the balance between insulin and glucagon in
a fasting state
in a feeding state
Fasting
- there needs to be sufficient glucose for maintnence of brain function and minimize how much depletion of the storage energy the body has (get glucose to brain)
Feeding
- promote storage of nutrietns and minizme relase of nutrients
minimal changes in glucose levels are the aim of homeostasis = narrow range 70-100
Glucagon
secretion & syntehsis
a counter-regulatory hormone for insulin which mobilizes stored glucose
- cells in pancrease secrete the preprohormone, its created into glucagon and is quickly broken down (no carrier protein bound to it) wthin teh blood stream
Stimulate Glucagon
- absencnce of insulin
- amino acids
- CCK, gastrin, GIP
- B adreg.
- exercise/stress
Inhibitors
- glucose
- somatostain
- GABA
- FFA, ketones
- insulin
Glucagons catabolic actions
within liver
- breaks down glycogen into glucose
- converts pyruvate into glucose
- released the glucose into the circulation
- uptake amino acids
in adipose
- release free fatty acids to converty to ketoacids with the production of energy
Role of Somatostatin
where does it come from
how long in serum
waht does it do
Delta cells in pancrease
direclty inhibtis both insulin and glucagon = to keep them both in check!!
short time in circulation = not bound
can also come from gut and pituitary
explain the glucose and glucagon response in obestiy
v normal
in normal gluocse/glucagon
- there is a natural rise and fall of the glucose level over a day (kept in check by insulin and glucagon)
- eraly on, obset individuals are able to compesate for the increase glucose in teh blood stream bu increasing insulin production - early on there is no insulin resistance
the B cells hypersecrete insulin to try to counter-act the high glucose
but there theres so much insulin, the rectpros doenregulated (tehyre overstimulated by the insulin) thus they no longer respond to the stimulus, and insulin resistance occurs
