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14 Cards in this Set

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  • Back
What is the mechanism of insulin production?
Insulin made as pre-propeptide-->pre sequence cleaved in ER-->C-peptide removed by proteases-->pro-insulin (mature) put into granule w/C peptide and a.acids-->released in response to HIGH glucose!
What is mechanism of insulin secretion?
Glucose increases-->transported into beta cells by Glut-2-->phosphorylated by glucokinase-->increases ATP levels-->ATP closes K+ channel-->Ca+ channel opens-->Ca enters cell-->activates kinases-->phosphorylate proteins leading to release of insulin.
How does insulin receptor (on target tissues) work?
Insulin travels to target tissue-->binds to receptor-->stimulates tyrosine phosphorylation of IRS and ShC

IRS-->binds/activates PI3-kinase-->phosphorylates several downstream kinases-->activates Akt

Akt-->increases Glut 4 transporters in cell membrane of muscle/adipose cells

Shc-->activates Ras-MAP kinase pathway-->growth.

--In some cases, insulin signaling activates kinases that activate phosphatases that de-phosphorylate metabolic enzymes
What are effects of insulin in liver?
Insulin is "anabolic"--wants to store things for later

Increases--Glycolysis (decreases gluconeogenesis), FA synthesis (decreases FA oxidation), TAG synthesis, VLDL release, glycogen synthesis (decreases glycogen breakdown), protein synthesis.
What are effects of insulin in adipose tissue?
"Anabolic"--wants to store things

Increases--glycolysis, fatty acid synthesis, TAG synthesis (decreases TAG hydrolysis), TAG uptake from chylomicrons, VLDL
What are effects of insulin in muscle?
"Anabolic"--wants to store things

Increases-->glycolysis, glycogen synthesis (decreases glycogen breakdown), protein synthesis.
How does glucagon receptor (on target tissues) work?
Glucagon receptor is coupled to G-protein (GPCR family)

Glucagon binds-->receptor replaces GDp w/GTP on Gas->Gas dissociates from beta/gamma subunits-->stimulates adenylate cyclase-->adenylate cyclase makes cAMP-->cAMP binds PKA, activating it-->PKA phosphorylates metabolic enyzmes, altering their activity->phosphorylates CREB, which regulates expression of metabolic enzyme genes
What are effects of glucagon in liver?
"Catabolic"--want to use stores!

Increases--Gluconeogenesis (decreases glycolysis), Glycogenolysis (decreases glycogen synthesis), Beta oxidation (decreases FA synthesis)
What are effects of glucagon in adipose tissue?
"Catabolic"--wants to use stores!

Increases--TAG hydrolysis (decreases TAG synthesis)
What are effects of glucagon in muscle?
--No glucagon receptors in muscle!
Describe Epinepherine
--"counter-regulatory hormone"
--Increases when blood glucose decreases (like glucagon) and during stress or danger.
--Binds to GPCR receptor (like glucagon)-->activates Gas-->increases cAMP levels just like glucagon!

-->While similar, Epi and glucagon can NOT bind to each other's receptors.
-->There are Epi receptors in muscle, NO glucagon receptors in muscle.
Describe effects of epinephrine in liver, adipose tissue, muscle..
Liver--same as glucagon.

Adipose--same as glucagon

Increase--Glycogenolysis AND glycolysis (decrease glycolysis)

Why does it increase both?
--glycogenolysis provides glucose (G6P)-->this glucose can be used for glycolysis.

So..decreases glycolysis in liver, so it MAKES glucose (not use it) for RBC's, brain, muscle. Increases glycolysis in muscle, so it can use its own glycogen stores for energy.
Describe cortisol
--"counter regulatory hormone"
--Increases when blood glucose decreases (like glucagon) and during stress or danger.
--steroid, hydrophobic, so will pass through cell membranes without receptor.
--goes inside cell-->binds to TF of genes encoding metabolic enzymes.
Describe effects of cortisol in liver, adipose tissue, muscle...
--increases gluconeogenesis

--increases TAG hydrolysis

--increases proteolysis
--decreases glucose uptake

OVERALL..cort wants to INCREASE blood glucose by increasing gluconeogenesis, using a.acids and glycerol.
--chronic stress-->cort causes loss of muscle mass and fat belly! maybe due to increased TAG hydrolysis-->FFA's are not broken down and put into fat.

Addison's-->cort deficiency.