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82 Cards in this Set

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5 hormones secreted by the pancreas:
-Insulin
-Glucagon
-Amylin
-Somatostatin
-Pancreatic Polypeptide
What are the 2 major tissue types of the pancreas?
-Acini
-Islets of Langerhans
Acini secrete _______
Islets secrete _______
Acini = digestive enzymes
Islets = digestive hormones
Where do the hormones secreted from islet cells go?
Into capillaries around which the islets are organized.
3 major cell types in islets of langerhans; what % is each?
-Beta = 60%
-Alpha = 25%
-Delta = 10%
What is secreted by each cell?
Alpha
Beta
Delta
PP
Alpha = glucagon
Beta = insulin + amylin
Delta = Somatostatin
PP = pancreatic polypeptide
What does Insulin inhibit?
Glucagon secretion
What does Amylin inhibit?
Insulin secretion
What does Somatostatin inhibit?
Secretion of both insulin and glucagon
Where else is SST made and released?
In the hypothalamus - it's the same polypeptide, just made in 2 different places.
What is the main stimulus for insulin secretion?
What does insulin secretion result in when there is carbohydrate excess?
Stimulus = Energy abundance - especially excess carbohydrates.
Result: storage of glycogen in liver and muscles.
What happens to additional excess carbs when no more glycogen can be stored?
They get stored in fat tissue.
What are the 3 effects of Insulin on protein metabolism during energy abundance?
-Promotes amino acid uptake
-Promotes AA conversion to protein
-Prevents protein breakdown
What is the initial form of insulin when synthesized?
Proinsulin
What does proinsulin consist of?
-A chain
-C peptide
-B chain
-2 disulfide bonds
What is C-peptide?
The peptide that connects the Bchain to the Achain
What creates Insulin?
Post-translational processing in which enzymes cleave the C-peptide.
So what gets released when one mole of insulin is secreted from the pancreas?
1 mol of C-peptide
So for a person that is producing no endogenous insulin, such as a person w/ Type I Diabetes, how could you tell?
There would be no c-peptide in the blood, because the exogenous therapeutic form of insulin doesn't have c-peptide.
What type of receptor is the Insulin receptor?
An enzyme-linked receptor
What is the insulin receptor made up of?
2 alpha subunits - extracellular
2 beta subunits - transmembrane
What happens when Insulin binds the extracellular alpha subunits of its receptor?
It causes autophosphorylation of the transmembrane B-subunit.
What does autophosphorylation of the beta subunit result in?
Tyrosine Kinase activity
What does receptor tyrosine kinase activity result in?
The activation of a phosphorylation cascade that activates or inhibits enzymes for metabolism.
What are the enzymes that are effected by insulin binding its tyrosine kinase receptor called?
Insulin receptor substrates (IRS)
What are 6 things affected by Insulin receptor activation?
-Glucose transport (Glut4)
-Protein synthesis
-Fat synthesis
-Glucose synthesis
-Growth/gene expression
-Brain control of hunger
Where does glucose uptake NOT increase when insulin is high?
In the brain - glucose transport is not controlled by insulin in the brain!!
What do muscle cells use for energy during most of the day when you're not eating?
Fatty acids
What causes muscles to use glucose after you eat?
Insulin which increases their permeability to glucose.
Is insulin the only thing that will allow the muscle cells to use large amounts of glucose?
No; exercising and the actual contraction of muscle increases its permeability to glucose too.
If you used one word for insulin what would it be? Why?
ANABOLIC
Because it induces storage of glucose, protein/fat synthesis, and glucose synthesis.
Does insulin secretion depend on what type of food you eat?
Nope; If you eat protein you want to store it. If you eat fat you want to store it. If you eat sugar you want to store it.
So what are the 3 main target tissues for insulin?
-Muscle
-Fat
-Liver
2 Anabolic effects of insulin on the Liver:
1. Glycogen storage
2. Glycolysis
2 Anticatabolic effects of insulin on the liver:
-Inhibits glycogenolysis
-Inhibits ketogenesis
-Inhibits gluconeogenesis
What are the 2 main things insulin does to muscle in general?
1. Promotes protein synthesis
2. Promotes glycogen synthesis
How does insulin promote protein synthesis in muscle? (2 ways)
1. Increases AA uptake
2. Stimulates protein synthesis via ribosomes
How does insulin promote glycogen synthesis in muscle? (3 ways)
1. Increases glucose transport
2. Enhances activity of glycogen synthetase
3. Inhibits activity of glycogen phosphorylase
Is muscle capable of take the phosphate off glucose-6-phosphate?
No; so it's NOT source of free glucose for gluconeogenesis.
How does insulin stimulate increased glucose uptake by muscle?
By increasing the concentration of glut4 transporters in the cells.
What does Insulin do to fat?
Promotes triglyceride storage
What are the 3 ways by which insulin promotes triglyceride storage in fat?
1. Induces lipoprotein lipase to make FA's available for absorption into fat cells
2. Increases glucose uptake
3. Inhibits lipolysis
So what happens when you have TOO MUCH insulin?
You get fat
What are the 4 stimulators of insulin secretion? Which is most important?
1. Glucose (most important)
2. Amino acids
3. Fatty acids
4. GH/Cortisol
How do GH and Cortisol stimulate Insulin?
Indirectly; when you're starving, cortisol is released and prevents glucose uptake in muscle so the blood glucose goes up. Islet cells respond appropriately to release insulin.
Is there a difference in giving oral glucose versus IV infusion?
YES!! Oral glucose goes through the GI tract and stimulates GI hormones that increase the GAIN of the islet cells so for every unit of glucose you get more insulin.
What do we call the GI hormones that increase the response of insulin to a sugar intake?
Amplifiers
What inhibits insulin secretion?
Somatostatin
What is the effect of SST on insulin secretion?
It DAMPENs the release; it buffers against wild insulin swings.
So what type of glucose transporter is found on islet beta cells?
Glut2
Is glut2 insulin sensitive?
ABSOLUTELY NOT - that would be like putting the cart before the horse.
What is the response of the beta cell to an increase in blood glucose?
1. Glu -> Glu6P via glucokinase
2. Gets burned to increase ATP
3. ATP close K channel, depolarizes cell, opens Ca channel
4. Ca influx allows insulin granules to dock/secretion occurs.
What do the alpha cells of the islets produce?
Glucagon
What are the target tissues of Glucagon?
-Liver
-Fat
What is the main role of Glucagon?
To increase gluconeogenesis
So why doesn't Glucagon effect muscle?
Because muscle doesn't DO gluconeogenesis.
In the liver what does Glucagon stimulate?
-Glycogenolysis
-Amino acid uptake
-FFa uptake
-Ketoacid synthesis
Why does Glucagon stimulate AA and FFA uptake in the liver?
Because you need them to make glucose
What does Glucagon inhibit in the liver?
Glycolysis
So during the fasting state when Insulin is LOW and Glucagon is HIGH what will be happening?
Insulin is preventing glucose uptake by muscles
Glucagon is preventing hypoglycemia by increasing blood glucose
What are 4 inhibitors of Glucagon release by alpha cells?
FIGS
-Free fatty acids
-Insulin
-Glucose
-Somatostatin
What is the type of inhibition of SST on glucagon?
The same as for insulin - it DAMPENS the secretion to prevent wild swings in hormone levels.
What do Amino acids do to glucagon?
STIMULATE THE RELEASE OF GLUCAGON
Why do amino acids stimulate the release of glucagon?
Because if you were a hyena living in Africa and you ate a HUGE meal of ONLY PROTEIN, if you didn't have glucagon you would become hypoglycemic because your blood sugar wouldn't increase, but insulin is still stimulated by AAs.
So amino acids stimulate:
-Insulin
AND
-Glucagon
What are Glucagon-like peptides?
GI hormones that are secreted from the gut in response to eating a meal
What is the acute effect of GLPs?
Increased gain of the islet beta cells so that when glucose comes along, more insulin is released.
When after feeding does GLP get released?
When food hits the stomach - long before glucose is absorbed.
What does GLP do in the chronic term?
Increases beta cell mass.
What is a good use of the chronic effect of GLPs to increase beta cell mass?
It helps type II diabetics overcome insulin resistance.
Also nauseates them so they don't eat so freaking much.
What flucutates more during a normal 24-hour period; glucagon or insulin? Why?
Insulin - because glucagon responds to starving states, and the average person doesn't starve if they eat 3 meals a day.
After you eat a meal, what is the insulin response like?
GLPs cause a big increase in insulin; then, while glucose is STILL high, insulin drops in response to SST and the waning of GLPs
Why is it SO IMPORTANT that insulin drops despite blood sugar still being high after a meal?
Because it prevents your blood sugar from going TOO low and making you become hypoglycemic.
So the 2 things that cause insulin to decrease after a meal:
1. Waning of GLPs
2. Increase in SST from the pancreas Delta cells to dampen the system
What is the process that occurs in the FED state?
1. Insulin goes up
2. Glucose uptake goes up in muscle fat and liver
3. Counterreg hormones are inhibited (Glucocorticoids and GH)
What is the process that occurs in the FASTED (starving) STATE?
1. Insulin is LOW
2. Counterreg hormones are HIGH
3. Glucose is produced by the liver
So what happens if there is no insulin?
There is no storage of glucose; it all spills into the urine and causes osmotic diuresis of very sweet pee.
So what happens when you give a normal person a blood glucose tolerance test?
Blood glucose goes up
CCK/GlP stimulates insulin
Glucose uptake occurs
Blood glucose returns to control.
What is the definition of hypoglycemia? Neuroglycopenia?
Hypo = <70
Neuro = <40-50
What happens to an abnormal person (diabetic) in a glucose tolerance test?
GI hormones still go up
Big HUUUUGE increase in blood sugar (no uptake in fat/muscle)
Takes forever to go back to control.
Why does the diabetic's blood sugar even go back down to ctrl?
Because it gets peed in the urine via osmotic diuresis.
What is Diabetes mellitus?
Too much sweet urine