Insulin Signalling

Question 1

What are the three main actions of insulin?

Answer 1

stimulates glucose uptake into the cell
turns off glucose production after a meal
stimulates glucose storage as glycogen

Question 2

What are some major diseases of signalling?

Answer 2

T2DM
heart disease
obesity
immune disease
neurodegeneration
cancer
epilepsy

Question 3

Why is intracellular communication important?

Answer 3

allows cells to respond to the environment and adjust to state of cell or tissue

Question 4

What type of receptor is the insulin receptor?

Answer 4

tyrosine kinase receptor

Question 5

How are the a and b subunits connected in the tyrosine kinase receptor?

Answer 5

di-sulphide bridges

Question 6

How are receptor tyrosine kinases defined?

Answer 6

by their ligands

Question 7

What type of second messenger does insulin primarily use?

Answer 7

lipids

Question 8

What does PI3K do?

Answer 8

specifically phosphorylates 3 position of ring on phosphatidyl-inositol

Question 9

what is the major PI3K reaction involved in insulin and GF signalling?

Answer 9

PIP2 to PIP3

Question 10

What does PTEN do?

Answer 10

convert PIP3 to PIP(4,5)2

Question 11

What does SHIP do?

Answer 11

convert PIP3 to PIP(3,4)2

Question 12

What does PIP3 activate?

Answer 12

Akt

Question 13

What does Akt activate?

Answer 13

fuel metabolism and storage
growth
proliferation
survival

Question 14

Where does PIP3 bind?

Answer 14

pleckstrin homology domains in proteins and alters their function

Question 15

Where can proteins get phosphorylated?

Answer 15

serine
threonine
tyrosine
on the hydroxyl groups

Question 16

What does protein phosphorylation do?

Answer 16

induce a large negative charge onto the structure

Question 17

What is the effect of protein phosphorylation

Answer 17

enzyme activation/inhibition
interaction with other proteins
cellular localisation
stability

Question 18

Give some examples of protein kinases that are oncogenes

Answer 18

Raf, Akt, abl

Question 19

What are the two pathways involved with insulin action?

Answer 19

PI3K pathway

MAPK pathway

Question 20

What are the two pathways involved with insulin action?

Answer 20

PI3K pathway

MAPK pathway

Question 21

What does PIP3 activate?

Answer 21

PDK1 - tyrosine kinases, adaptor proteins, GTPases, GDP/GTP exchange

Question 22

What does PDK1 activate?

Answer 22

PKB, p70S6K, PKC and SGK

Question 23

How is PKB activated?

Answer 23

phosphorylated on Thr308 by PDK1 and on Ser473 by mTORC2

Question 24

How many isoforms of PKB are there?

Answer 24

3

Question 25

What does IRS activate in the MAPK pathway?

Answer 25

Grb2/mSOS

Question 26

What does Grb2/mSOS activate?

Answer 26

stimulates Ras-GDP for Ras-GTP exchange

Question 27

What does Ras-GDP for Ras-GTP exchange do?

Answer 27

activates Raf

Question 28

What does Raf activation do?

Answer 28

Activates MAPKKinase

Question 29

What does phosphorylation of MAPKK do?

Answer 29

activates p42/p44 MAPK

Question 30

What does p42/p44 MAPK signalling aid in?

Answer 30

neuronal structure | Gene transcription and growth

Question 31

What does PKB activation result in?

Answer 31

gluconeogenic inhibition GSK3 phosphorylation phosphorylation of p70S6K GLUT 4 translocation

Question 32

What turns off insulin signalling?

Answer 32

MAPK phosphatase

Question 33

What kinds of treatments are being looked at for insulin resistance in diabetics?

Answer 33

PTP-1B inhibitors GSK3 inhibitors AMPK activators

Question 34

How would GSK3 inhibitors work?

Answer 34

artificially restore the effect of insulin

Question 35

What does reduced insulin sensitivity result in?

Answer 35

increased insulin production to compensate

Question 36

What are some complications of T2DM?

Answer 36

``` retinopathy neuropathy nephropathy stroke heart failure ```