Pancreas: Histo and Phys (Nutting) Flashcards
What islet cells secrete insulin?
beta
What islet cells secrete glucagon?
alpha
What islet cells secrete somatostatin?
delta
What islet cells secrete peptide polypeptide?
F cells
inhibits both glucagon and insulin
somatostatin
describe the cellular organization in an islet
roughly~ alpha cells on outside with beta cells in middle and delta cells in-between beta cells
proinsulin → insulin + _____
C-peptide
Islets are separated from the ______ by a fine fibrous capsule that extends into the islet together with blood vessels
exocrine cells
round oval islets vs trabecular, irregular in shape islets
beta cell rich are rounder
pancreatic peptide rich are irregular
What part of the pancreas are the trabecular, irregular islets that secrete PP found?
posterior part of the pancreatic head
contains secretory acini
exocrine cells of pancreas
picks up exocrine secretions, to the islet secretions bc they go to capillaries
duct of the exocrine pancreas
____ cells occupy 65-70% of the islet volume!
beta
**take away is that beta»_space; alpha volume
function of pancreatic polypeptide
self regulates the pancreas secretory activities (endocrine and exocrine)
affects hepatic glycogen levels and GI secretions
**DJ talked about it as being *anorexigenic and ↑ conc after a meal
What decreases PP secretion?
somatostatin and IV glc
What increases PP secretion?
eating protein meal
fasting
exercise
acute hypoglygemia
describe the structure of proinsulin moleucle
a chain and B chain attached via 2 disulfide bonds with C peptide between them
at 2 locations, there are a pair of basic aa that are cleaved to release C-peptide and insulin
Pro insulin is converted into the mature hormone by the combined action of …
Where in the cell does this occur?
two endoproteases and a carboxypeptidase E
Secretory vesicles
Why is C-peptide used to measure islet function in pts treated with exogenous insulin?
cannot measure insulin bc you do not know how much the pt has made and how much is exogenous. Tells you how many islet cells may be left/have residual function
Describe the process of insulin synthesis
- signal peptide translocates translated protein into the ER
- folding and oxidation (and signal seq cleavege) in ER
- ER → golgi → vesicle
- in vesicle, proteases cleave/liberate C peptide
- carboxypeptidase E produces mature insulin
Stimuli for increased and decreased insulin secretion:
Inc secretion: ↑ plasma glc ↑ plasma aa ↑ FA, ketones ↑ inc GI hormones, mainly GIP, GLPs) ↑ GH ↑ Cortisol ↑ Ach (parasympathetics) ↑ glucagon *GGGG AAFC
Decreased secration:
↑ Epi, NE (sympathetics)
↑ somatostatin
Stimuli for increased and decreased glucagon secretion:
Increased secretion: ↑ plasma aa ↑ Ach ↑ epi, NE (sympathetics) ↑ VIP ↑ CCK *VAACS
Decreased section: ↑ plasma glc ↑ insulin ↑ somatastatin ↑ FFA, ketones *FIGS
Why does an ↑ in plasma aa signal glucagon to be released?
to prevent sudden hypoglycemia if you eat a high protein meal without carbs
where is insulin degraded?
liver and kidneys by insulinases
Where is glucagon degraded?
liver
Where in the body does insulin exert the majority of its action?
liver, that is where it goes first
muscle
adipose
Where in the body does glucagon exert the majority of its action?
liver, that is where it goes first and it is then degraded there ∴ periphery has very low [glucagon]
what additional action will glucagon have at high conc?
lipolytic
→ takes high conc to get to periph to have this effect, usually it is localized to the liver bc it is degraded there
how do PERIPHERAL glucagon levels change in response to a meal?
peripherally it does NOT change (and is LOW)
levels fluctuate in pancreas in response to food
What does insulin stimulate in many tissues?
glc uptake and utilization
How is glc “utilized” in cells?
- make ATP
- make glycogen
- make TAG
in what cells/tissue will insulin NOT stimulate glc uptake
brain (*except part of hypothalamus)
intestinal mucosa
RBCs
Kidney tubules
What is the only part of the brain that insulin will stimulate glc uptake?
hypothalamus
speed and duration of action of glucagon vs insulin
both act fast and decrease in conc quickly after action
glucagon complements the effects of what substances? WHY?
Epi and NE bc is is best to not be hypoglycemic, we need energy! ∴ they can substitute for each other = redundancy!!
how does glucagon maintain normal glc conc
promotes glc release from the liver
what effects does glucagon have on the liver?
↑ glycogenolysis
↑ aa uptake → gluconeogenesis
↑ ketoneogenesis (TAG → KB for energy)
What is needed for glucagon to be synthesized in the liver
corstiol
What enzymes does glucagon effect?
↑cAMP and PKA to.. ↑ phosphorylase → glycogenolysis ↓ glycogen synthase ↓ F-2,6,6-BP = ↑gluconeogenesis and ↓glycolysis ↓ PK activity to ↓pyruvate/AcCosA→TAG
____ is the most potent hormone
insulin
insulin is anabolic or catabolic hormone?
anabolic (and anti-catabolic)
*promotes synthesis of storage forms and inhibits breakdown from these stores
= Stimulates building up while inhibiting breakdown!
What effects does insulin have in muscle?
↑ glc uptake
↑ aa uptake
↑ LPL synthesis (extracts FA from VLDL and CMs for energy)
↓ protein breakdown and aa release
(↑ protein synthesis, may or may not)
What effects does insulin have in adipose?
↑ glc uptake
↑↑↑ TAG synthesis
↑ FA synthesis (glc → pyruvate→ AcCoA → malonylCoA →LCFA)
↑ LPL activity
↓↓↓ lipolysis
What effects does insulin have in liver?
↑ TAG synthesis
↑ protein synthesis
↓ VLDL and apoB synthesis
↓ glc release
↓ ketogenesis
insuilin ↑ or ↓ activity of hormone sensitive lipase
↓
What effect will high levels of GH and cortisol have on muscle and fat cells (in terms of insulin activity)
they become insulin resistant
what increases the sensitivity of the body to hyperglyemia
GH, cortisol, and T3 → insulin more readily released
In terms of biochem mechs, how does insulin increase glc uptake by muscle and adipose?
insulin binds receptor and stimulates translocation of glc transporter proteins from vesicles to surface of PM
