Insulin Signalling Flashcards Preview

E: Regulatory Physiology & Pharmacology > Insulin Signalling > Flashcards

Flashcards in Insulin Signalling Deck (44):
1

When is diabetes diagnosed?

When blood glucose levels are not controlled properly

Hypergylcemia

2

Insulin?

Major hormone

Prevents hyperglycemia and therefore diabetes

 

3

Hyperglycemia?

High blood glucose levels in the body

4

Major function of insulin?

To prepare the body for incoming nutrients 

Promoting storage, thereby preventing nutrient toxicity

5

What 3 processes does insulin do within the cell?

Insulin stimulates glucose uptake into the cell.

Turns off glucose production after a meal.

Stimualtes glucose storage as glycogen

6

7 Major diseases caused by insulin signalling?

Type 2 diabetes: defective insulin signalling.

Heart disease: abnormal vascular signalling

Obesity: abnormal appetitie and thermogenesis

Immune disease: defective immunoreactivity.

Neurodegeneration: abnormal apoptosis

Cancer: abnormal growth signal

Epilepsy: abnormal neuronal signalling

7

The process of signalling?

External signal: such as hormone or neurotransmitter- transfers info between cells.

Receptor: functions to detect the external signals.

Transducer: Receives info from receptors and transform it into different types of info.

Effectors: Specific cellular process. 

8

Why is intracellular communication needed?

Respond to environemnt

Adjust to state of cell/tissue (DNA damage, cell cycle etc)

9

What is an insulin receptor?

Tyrosine kinase associated receptor

Membrane bound. 

alpha and beta domains.

10

Receptor tyrosine kinase classes are defined by?

How many classes are there?

Defined by their ligands

Lots and lots of classes

eg. EGF, FGF, Insulin

11

Reaction to get from ionositol into phosphoinositide and then into PI kinase?

Inositol -----(ATP->ADP)---> Phosphoinositols

Phosphoionositides-------(ATP->ADP)----->PI Kinase

 

Specifically phosphorylates 3-position of ring.

12

PI3-kinase used as?

Used to phosphorylate different phosphatidyl inositols. 

 

PIP2-> PIP3

This is the major reaction involved in insulin and GF signalling

13

What two enzymes are in balance for the ratio PIP2:PIP3?

 

PI3-kinase

PTEN (lipid phosphatase)

Additionally SHIP (5-Ppase)

14

Name some of the physiological agents that induce PIP3 levels?

EGF

FGF

GH

Insulin

Leptin

IGF-1

15

What does PIP3 bind to?

 

Binds to the PH domain

Alters their function

16

Protein phosphorylation?

Key to transucing insulin action.

Reversible method.

 

17

What group can proteins get phosphorylated on?

Any hydroxyl group

Introduces a large negative charge into the protein structure

18

Serine/Threonine Protein Kinases?

Primarily cytosolic and nuclear.

 

19

Tyrosine Protein Kinases?

Primarily receptor linked

20

Dual specifcity protein kinases?

Small number of protein kinases

Can phosphorylate Ser/Thr or tyrosine. 

21

Effects of protein phosphorylation?

Enzyme activation/inhibition

Interaction with other proteins.

Cellular localisation

Stability

22

What other conditions do specific protein kinase inhibitors treat?

Cancer

Early trials: immunological, metabolic and neurological diseases.

For the treatment for insulin resistance

23

the two specific pathways involved in insulin action?

1) PI3- kinase pathway

2)  MAP kinase pathway

24

What is the P13-kinase pathway?

Insulin binds to receptor

Causing a phosphorylation effect on the receptor.

This allows IRS to bind and become activated (by phosphorylation)

This binds to PI3-K which activates it.

Stimualtes the PIP2 to PIP3 reaction

25

What is the outcome of producing PIP3

Produces downstream effects

Such as PDK1

GTPases

GDP/GTP exchange.

Adaptor proteins

Tyrosine kinase

26

PDK1 regulates?

Insulin activation of protein kinase B (AKT)

 

 

27

Protein Kinase B (AKT)

Major enzyme in PIP3 signalling.

Key component of insulin and GF.

28

MAP kinase Signalling?

Insulin binds to receptor.

Phosphorylation of the receptor.

Causes the IRS to bind.

Activates GRB2:mSOS.

This stimulates the activation of Ras (using ATP)

Activation of Raf

Activation of MAPKK (by phosphorylation)

Stimulates the activation of p44MAP kinase

29

MAP kinase does?

Stimulation of downstream affectors.

Gene transcription growth (including CREB, MSK)

Neuronal strcuture: MAP2

30

AKT effects?

Inhibits:

GSK3 (an inhibitor of the glycogen synthesis)

Glyconeogenic gene expression

Stimulates:

GLUT4 translocation.

Protein translation

31

Protein tyrosine phosphatase 1B?

Turns off the insulin signalling

By interferring with the MAP kinase and PI3 kinase pathway

32

Negative feedback within MAP kinase pathway?

Downstream production of MAPK phosphatas

Inhibits the MAPK.

33

Type 2 diabetes are found to have what wrong with these pathways?

Defective insulin signalling.

Could be due to insulin antagonist (PTP1B, IRS1 kinase)

34

What causes PIP3 to break down to PIP2?

PTEN

Lipid phosphatase

35

Insulin resistance

Reduced sensitivity to insulin

Molecular, cellular , tissue or whole organism

36

Therapy to fix and re-sensitive to insulin

Need a good diagnosis on what has went wrong as there is numerous reasons why someone has become insulin resistant.

37

Naem the 3 Regulators of insulin signalling ?

Why are they important?

  1. PTP1B inhibitors
  2. GSK-3 inhibitors
  3. AMPK activators

Important for current research to overcome insulin resistance

38

What does PTP1B do?

Turns off insulin signalling.

Therefore no longer MAP kinase or PI3 kinase pathway

39

Inhibitors of PTP1B activity?

Increase the insulin receptor activity.

Being developed for the treatment of diabetes.

 

40

GSK3 inhibitors?

Being developed for the treatment of diabetes.

Restore the effect of insulin on GSK3 activity. 

41

Insulin and diabetes?

In diabetes there is a reduced insulin sensitivity

Leads to enhanced insulin production to compensate.

Asymptomatic: no symptoms.

42

When can type 2 diabetes be diagnosed?

When the pancreas can no longer make enough insulin to overcome the insulin resistance.

43

Difference between type 1 and type 2 diabetes?

The pre-diabetes stage.

T2 patients have relatively high levels of insulin but the cells are resistant to it while T1 patients make little insulin.

 

44

What are the risk factors for T2 diabetes?

Environmental

Diet

Exercise

Obesity.