Insulin Signalling

Question 1

Name 5 things insulin has effect on in diff time frames

Answer 1

Glycogen synthase stimulation

Aa transport

Ion flux regulation

Regulation of txn

Stimulates cell division

Question 2

What effects of insulin take hours

Answer 2

Cell division and regulation of txn

Question 3

Insulin has long and short effects. What is this called

Answer 3

Acute and chronic

Question 4

Does insulin only work at nucleus eg for gene txn

Answer 4

No , can work at membrane to have effect eg glut4

Question 5

How many insulin need to bind receptor

Answer 5

1 because already dimerised

Question 6

What produces preproinsulin

Answer 6

B cells

Question 7

What happens to pre pro insulin 81-86 aa in the er

Answer 7

Gets cleaved and folded into a 51 aa chain and forms 3 ss bonds

Question 8

What is the new folded, bonded 51 aa insulin called from er

Answer 8

Proinsulin

Question 9

What acts on proinsulin 51aa in the Golgi

Answer 9

Carboxypeptidase e

Pro hormone convertases 1 and 2

Question 10

What are carboxypeptidases and prohormoone convertases for

Answer 10

Release c peptide forming insulin

Question 11

What is insulin stored with

Answer 11

Stored with zinc in secretory granules

Question 12

What does insulin release due to hyperglycaemia block

Answer 12

Glucagon release from a cells

Question 13

What causes insulin release

Answer 13

Glucokinase starting glycolysis

When glucose enters B cell via glut2 glucokinase starts glycolysis

The production of atp blocks k channels and causes depolarisation

Ca voltage channels open and ca floods in

Secretory granules with insulin fuse with membrane

Question 14

Explain structure of insulin receptor

Answer 14

A and b subunits dimer

A has the insulin ligand bs

Held to eachother by s-s between a-a and each a-b = 3 ss bonds

Question 15

Tyrosine residues on the tk domain of b subunits get phosphorylated, what effects do these have

Answer 15

Can cause irs binding , or stimulate kinase activity

Question 16

What do ser/thr residues on b subunits stop

Answer 16

Block kinase activity

Question 17

Which tyr allows irs binding

Answer 17

T960

Question 18

There are 2 types of irs what’s the difference

Answer 18

Different regulation eg diff phos of ser/thr to block them

Question 19

Which residue gets phos to activate irs

Answer 19

Tyrosine

Question 20

Which domains of other proteins bind residues of Irs specifically

Answer 20

Sh2 of grb2 and pi3k

Question 21

Which domain of irs binds phosphorylated tyrosine residues of insulin receptor

Answer 21

Phosphotyrosine binding PTB

Question 22

What is the ph domain

Answer 22

Binds phosphoinositol in lipids of membrane

Question 23

How is sh2 specific for binding of proteins to irs docking protein

Answer 23

Phosphotyrosine residues of irs are flanked by specific aa sequences recognised by either grb2 or pi3k sh2

Question 24

What is sh3 on grb2

Answer 24

Binds proline regions of sos guanine exchange factor

Question 25

Explain the steps of the Ras pathways

Answer 25

Grb2 sh2 binds pt residues of irs Sh3 domain binds sos Sos exchanges ras gdp for gtp Ras activates raf mapkkk Phos of Mek mapkk Phos of erk mapk

Question 26

What is the Ras pathway for

Answer 26

Differentiation, growth, survival

Question 27

What does irs activate in the Ras independent path via sh2

Answer 27

Pi3k

Question 28

What does pi3k phosphorylate in membrane

Answer 28

I bisphosphate forming pi3 - 4,5 phosphoinositol triphosphate Which then activates akt (pkb) via phosphorylation

Question 29

How does akt affect glucose uptake of adipocytes and liver

Answer 29

Glut4 vesicles activation

Question 30

How does akt allow glycogen synthase activation

Answer 30

Phosphorylates glycogen synthase kinase which inactivates its action of GS

Question 31

What target of akt allows protein synthesis to block high BGC

Answer 31

Mtor

Question 32

What gets activated to block lipolysis and release of free fa/glycerol

Answer 32

Pde3b

Question 33

What does pde3b do

Answer 33

Block action of HSL which causes lipolysis eg triacylgycerol lipase

Question 34

What happens to free fa to allow production of acetyl coa

Answer 34

B oxidation

Question 35

What effects does glucagon have produced by a cells to increase BGC

Answer 35

Reduced glycogenesis and glycolysis Increased gluconeogenesis and glycogenolysis and lipolysis

Question 36

What type of receptor is glucagon receptor and what secondary messengers is activated

Answer 36

Gpcr Activates the ac so camp and pka activation

Question 37

How does pka block glycogenesis

Answer 37

It can phosphorylate glycogen synthase to block it

Question 38

Which tf for gluconeogenesis is activated by pka

Answer 38

Creb

Question 39

What 2 enzymes for gluconeogenesis increased by creb tf

Answer 39

Glucose 6 phosphatase Phosphoenolpyruvate pep kinase (oxaloacetate into pep)

Question 40

Other than creb how does pka allow increased glucose via glycogenolysis

Answer 40

Activates glycogen phosphorylase

Question 41

How is glycolysis blocked by glucagon

Answer 41

Reduced pfk so less fructose 1,6 bis production

Question 42

Which enzyme is activated to release free fa and glycerol in glucagon signal = lipolysis

Answer 42

Triacylglycerol lipase (triacylglycerol to diacylglycerol)

Question 43

How is free fa balance important and blocked in diabetes bc of no insulin

Answer 43

Free fa can be b oxidated back into acetyl coa acetyl coa allows tca progression Too much acetyl coa blocks glucose conversion to pyruvate so increases glucose (because blocks pyruvate dehydrogenase) Also increases citrate through tca which blocks Pfk for glycolysis = more glucose, no energy