EXAM3_L29_Metabolic_Signaling

Question 1

How does Glucagon signaling work/increase PKA activity?

Answer 1

GalphaS GPCR increases cAMP-> Increases PKA activity

Question 2

What two ways does insulin decrease PKA activity?

Answer 2

1. protein phosphatase-1 (dephosphorylates PKA substrates)

2. insulin-responsive cAMP phosphodiesterase (less cAMP, less PKA)

Question 3

What does insulin and glucagon do to PKA activity respectively?

Answer 3

Insulin- decreases PKA (two ways)

Glucagon- increases cAMP thus PKA activity

Question 4

Insulin signaling via IRS1- Two events when insulin binds RTK:

Answer 4

UPON INSULIN SIGNAL: (insulin binds RTK):

1. IRS1 binds GRB2 > MAPK (cell division, survival)
2. IRS1 bind PI3K> AKT (increase glucose uptake GLUT4)

akt-also alters metabolic enzyme activities

Question 5

What is the assumption of a defective IRS-1 signaling pathway?

Answer 5

• Consequence of obesity

- can result in insulin resistance and diabetes

Question 6

What is the newly phosphorylated domain of IRS-1?

what two things bind to this domain?

Answer 6

• SH2 domain (src homology 2)
• can bind to : GRB2 or PI3K

GRB2 >SOS> MAPK pathways
PI3K (pi3 kinase)>activates AKT pathway

Question 7

What are the 4 counterregulatory Hormones?

What do they do?

Answer 7

Oppose action of insulin by mobilizing fuels into blood

• Glucagon
• Cortisol
• Epinephrine
• Norepinephrine

Question 8

What hormones are stress released in response to neuronal signals?

What is the signal pathway for these from the brain?

Answer 8

Cortisol (adrenal cortex)
Epinephrine (adrenal medulla)
Norepinephrine (adrenal medulla)

Hypothalamus>Pituitary>ACTH>Adrenal Gland

Question 9

When you exercise, or experience HYPOGLYCEMIA, hypoxia, or hemorrhage what neurotransmitter will be released? What affects will it have on IG ratio?

Answer 9

Epinephrine- catecholamine (from tyrosine)

• Decreases IG ratio
• increases and mobilizes fuel/energy into blood

Question 10

Cortisol is a glucocorticoid derived from Cholesterol (adrenal cortex) - why is that significant?

Answer 10

Cortisol binds receptors INSIDE THE CELL

-steroid diffuses right through plasma membrane

Question 11

Cortisol functions differently in Adipose, Muscle, and Liver

What does it do in each?

Answer 11

Adipose- lipolysis (provides energy for liver gluconeogenesis)

Muscle- Decreases GLUT4 uptake of glucose

Liver- Gluconeogenesis (increase glucose production)

Question 12

Why do Dietary Amino Acids stimulate Insulin High glucose and low glucose states?

Answer 12

High glucose state- AA’s convert to glucose> insulin

Low glucose state- AA’s from high protein diet can be made into glucose and stimulate a little insulin to prevent muscle breakdown

Question 13

Is fat ever used to make glucose?

Answer 13

NOPE

Question 14

What affects of glucagon in muscle, liver, adipose?

Answer 14

LIVER ONLY (only gasGPCR receptors on Liver Cells)

• mobilizes nutrient molecules,
• glycogenolysis (glycogen breakdown for export)
• gluconeogenesis for export (using AA’s as C source not FA’s)

Question 15

Glucagon receptors are only found on Liver cells
(for liver glycogen breakdown) and will not affect the stored glycogen in muscle cells.

How is Muscle glycogen used then?

Answer 15

Epinephrine stimulates glycogenolysis of muscle glycogen to be used ONLY FOR THE MUSCLE ITSELF

Question 16

What is muscle glycogen used for?

Answer 16

Only used for its own glycogenolysis>glucose

NEVER USED FOR BLOOD GLUCOSE HOMEOSTASIS!

Question 17

How does epinephrine affect Muscle, Adipose, Liver, Pancreas?

Answer 17

Muscle- glycogenolysis (glycogen>glucose) MUSCLE USE

Liver- glycogenolysis (glycogen>glucose) for EXPORT

Adipose- FA’s mobile for use

Pancreas- Increases alpha cell (glucagon secretion)
inhibits beta cell (insulin secretion)

Question 18

What does the liver use for energy?

What does it never use?

Answer 18

Beta oxidation of FAT

NEVER USES GLYCOGEN (exported to brain & RBCs)

Question 19

How are blood glucose levels maintained when fasting?

Answer 19

Gluconeogenesis (from aa’s to glucose)

Glycogenolysis (glycogen to glucose) while supplies last

Question 20

Stress or Low IG ratio in Liver?

Answer 20

glucagon and Epinephrine:

• gluconeogenesis
• glycogenolysis
• ketone bodies

Question 21

High IG ratio in Liver?

Answer 21

Insulin:
glycogenesis
lipogenesis

Question 22

Where are ketone bodies only made?

Answer 22

KB Made in Liver (can’t be used in liver) Used by other cells only

Question 23

High IG ratio in Adipose?

Answer 23

Insulin:
LIPOGENESIS
Glucose Uptake (GLUT4)

FFA synthesis in liver stored TAGs in adipose
-(glucose>glycerol)

Question 24

When will Lipolysis occur in adipose tissue?

Answer 24

ONLY EPINEPHRINE (stress only)

-TAGs of adipose mobilized into FFA’s in circulation

Stress( HYPOGLYCEMIA, Hypoxia, exercise, Hemorrhage, pain)

Question 25

Low IG ratio in adipose?

Answer 25

No affect! - - NO GLUCAGON RECEPTORS - only has epinephrine receptors (lipolysis will only occur during stress/epinephrine signaled

Question 26

High IG ratio in muscle?

Answer 26

Insulin: -AMPK> GLUT4 glucose uptake -Glycogenesis* (store glucose as glycogen) * this glycogen can only be used in the muscle * only used when epinephrine/stress induced note: AMPK glucose is metabolized, and not stored

Question 27

How much glucose goes to the muscles after a meal?

Answer 27

80%

Question 28

Low IG ratio in muscle?

Answer 28

NO EFFECT! - no glucagon receptors on muscles (only has epi receptor) -glycogenolysis occurs via epinephrine/stress only!

Question 29

What is important about glucose that enters the muscle as AMPK?

Answer 29

It is metabolized and not stored as glycogen!

Question 30

Stress to muscle cells? | exercise, hemorrhage, HYPOGLYCEMIA, Hypoxia, Pain)

Answer 30

Epinephrine

Question 31

Insulin stimulates glucose uptake in the muscles via GLUT4. | When insulin is low or signal impaired, GLUT4 can still be stimulated by what pathway?

Answer 31

AMPK (activated protein kinase) pathway

Question 32

small rise in AMP has what effect compared to ATP?

Answer 32

an AMP increase has much bigger increase in activity than equivalent amount of ATP increase

Question 33

What does Adenylate Kinase do?

Answer 33

takes 2 ADPs and makes an ATP

Question 34

AMP increases AMPK by what two ways?

Answer 34

1. Allosteric activates AMPK (5x greater activity) | 2. Stim phosphorylation of AMPK (100x greater activity)

Question 35

What is Metformin?

Answer 35

Most common Type II Diabetes medication - Allows GLUT4 to uptake glucose in the muscles - increases AMP and> AMPK activation - AMPK benefits independent of insulin signaling

Question 36

What are the benefits of metformin on blood glucose levels?

Answer 36

- increases uptake of glucose in the muscle (GLUT4) - stops gluconeogenesis in liver *Independent of insulin signaling

Question 37

What are the benefits of metformin on blood lipid levels?

Answer 37

promotes beta oxidation rather than storage - Reduces TAGS in circulation - improves insulin sensitivity