Insulin Signalling Flashcards

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1
Q

Name 5 things insulin has effect on in diff time frames

A

Glycogen synthase stimulation

Aa transport

Ion flux regulation

Regulation of txn

Stimulates cell division

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2
Q

What effects of insulin take hours

A

Cell division and regulation of txn

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3
Q

Insulin has long and short effects. What is this called

A

Acute and chronic

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4
Q

Does insulin only work at nucleus eg for gene txn

A

No , can work at membrane to have effect eg glut4

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5
Q

How many insulin need to bind receptor

A

1 because already dimerised

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6
Q

What produces preproinsulin

A

B cells

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7
Q

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

A

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

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8
Q

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

A

Proinsulin

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9
Q

What acts on proinsulin 51aa in the Golgi

A

Carboxypeptidase e

Pro hormone convertases 1 and 2

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10
Q

What are carboxypeptidases and prohormoone convertases for

A

Release c peptide forming insulin

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11
Q

What is insulin stored with

A

Stored with zinc in secretory granules

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12
Q

What does insulin release due to hyperglycaemia block

A

Glucagon release from a cells

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13
Q

What causes insulin release

A

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

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14
Q

Explain structure of insulin receptor

A

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

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15
Q

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

A

Can cause irs binding , or stimulate kinase activity

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16
Q

What do ser/thr residues on b subunits stop

A

Block kinase activity

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17
Q

Which tyr allows irs binding

A

T960

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18
Q

There are 2 types of irs what’s the difference

A

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

19
Q

Which residue gets phos to activate irs

A

Tyrosine

20
Q

Which domains of other proteins bind residues of Irs specifically

A

Sh2 of grb2 and pi3k

21
Q

Which domain of irs binds phosphorylated tyrosine residues of insulin receptor

A

Phosphotyrosine binding PTB

22
Q

What is the ph domain

A

Binds phosphoinositol in lipids of membrane

23
Q

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

A

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

24
Q

What is sh3 on grb2

A

Binds proline regions of sos guanine exchange factor

25
Q

Explain the steps of the Ras pathways

A

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

26
Q

What is the Ras pathway for

A

Differentiation, growth, survival

27
Q

What does irs activate in the Ras independent path via sh2

A

Pi3k

28
Q

What does pi3k phosphorylate in membrane

A

I bisphosphate forming pi3 - 4,5 phosphoinositol triphosphate

Which then activates akt (pkb) via phosphorylation

29
Q

How does akt affect glucose uptake of adipocytes and liver

A

Glut4 vesicles activation

30
Q

How does akt allow glycogen synthase activation

A

Phosphorylates glycogen synthase kinase which inactivates its action of GS

31
Q

What target of akt allows protein synthesis to block high BGC

A

Mtor

32
Q

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

A

Pde3b

33
Q

What does pde3b do

A

Block action of HSL which causes lipolysis eg triacylgycerol lipase

34
Q

What happens to free fa to allow production of acetyl coa

A

B oxidation

35
Q

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

A

Reduced glycogenesis and glycolysis

Increased gluconeogenesis and glycogenolysis and lipolysis

36
Q

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

A

Gpcr

Activates the ac so camp and pka activation

37
Q

How does pka block glycogenesis

A

It can phosphorylate glycogen synthase to block it

38
Q

Which tf for gluconeogenesis is activated by pka

A

Creb

39
Q

What 2 enzymes for gluconeogenesis increased by creb tf

A

Glucose 6 phosphatase

Phosphoenolpyruvate pep kinase (oxaloacetate into pep)

40
Q

Other than creb how does pka allow increased glucose via glycogenolysis

A

Activates glycogen phosphorylase

41
Q

How is glycolysis blocked by glucagon

A

Reduced pfk so less fructose 1,6 bis production

42
Q

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

A

Triacylglycerol lipase (triacylglycerol to diacylglycerol)

43
Q

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

A

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