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Regulatory Physiology and Pharmacology > Insulin Signalling > Flashcards

Insulin Signalling Flashcards

1
Q

What are the three main actions of insulin?

A

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

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2
Q

What are some major diseases of signalling?

A 
T2DM
heart disease
obesity
immune disease
neurodegeneration
cancer
epilepsy
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3
Q

Why is intracellular communication important?

A

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

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4
Q

What type of receptor is the insulin receptor?

A

tyrosine kinase receptor

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5
Q

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

A

di-sulphide bridges

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6
Q

How are receptor tyrosine kinases defined?

A

by their ligands

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7
Q

What type of second messenger does insulin primarily use?

A

lipids

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8
Q

What does PI3K do?

A

specifically phosphorylates 3 position of ring on phosphatidyl-inositol

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9
Q

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

A

PIP2 to PIP3

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10
Q

What does PTEN do?

A

convert PIP3 to PIP(4,5)2

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11
Q

What does SHIP do?

A

convert PIP3 to PIP(3,4)2

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12
Q

What does PIP3 activate?

A

Akt

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13
Q

What does Akt activate?

A

fuel metabolism and storage
growth
proliferation
survival

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14
Q

Where does PIP3 bind?

A

pleckstrin homology domains in proteins and alters their function

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15
Q

Where can proteins get phosphorylated?

A

serine
threonine
tyrosine
on the hydroxyl groups

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16
Q

What does protein phosphorylation do?

A

induce a large negative charge onto the structure

17
Q

What is the effect of protein phosphorylation

A

enzyme activation/inhibition
interaction with other proteins
cellular localisation
stability

18
Q

Give some examples of protein kinases that are oncogenes

A

Raf, Akt, abl

19
Q

What are the two pathways involved with insulin action?

A

PI3K pathway

MAPK pathway

20
Q

What are the two pathways involved with insulin action?

A

PI3K pathway

MAPK pathway

21
Q

What does PIP3 activate?

A

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

22
Q

What does PDK1 activate?

A

PKB, p70S6K, PKC and SGK

23
Q

How is PKB activated?

A

phosphorylated on Thr308 by PDK1 and on Ser473 by mTORC2

24
Q

How many isoforms of PKB are there?

A

3

25
Q

What does IRS activate in the MAPK pathway?

A

Grb2/mSOS

26
Q

What does Grb2/mSOS activate?

A

stimulates Ras-GDP for Ras-GTP exchange

27
Q

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

A

activates Raf

28
Q

What does Raf activation do?

A

Activates MAPKKinase

29
Q

What does phosphorylation of MAPKK do?

A

activates p42/p44 MAPK

30
Q

What does p42/p44 MAPK signalling aid in?

A

neuronal structure

Gene transcription and growth

31
Q

What does PKB activation result in?

A

gluconeogenic inhibition
GSK3 phosphorylation
phosphorylation of p70S6K
GLUT 4 translocation

32
Q

What turns off insulin signalling?

A

MAPK phosphatase

33
Q

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

A

PTP-1B inhibitors
GSK3 inhibitors
AMPK activators

34
Q

How would GSK3 inhibitors work?

A

artificially restore the effect of insulin

35
Q

What does reduced insulin sensitivity result in?

A

increased insulin production to compensate

36
Q

What are some complications of T2DM?

A 
retinopathy
neuropathy
nephropathy
stroke
heart failure

Regulatory Physiology and Pharmacology (14 decks)

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