MCB Lecture 17 The Post-Prandial state

Question 0

What does F-F-F bring about?

Compare the muscles and the liver

Answer 0

Muscles: glycolysis, glycogenolysis

Liver: glycogenolysis, gluconeogenesis

Question 1

What is the Fright-Flight-Fright response? Where does it target?

Answer 1

This is enacted in times of stress
Fright: adrenaline released
Flight, fight: glycogenolysis, gluconeogenesis

Question 2

How does glycogenolysis activation differ in the liver and the muscles?

Answer 2

It’s the same

Question 3

What are the differences between adrenaline pathways in muscle and liver? (2)

Answer 3

1. In the muscles, pyruvate kinase is not deactivated (because it doesn’t have the Serine residue
2. Adrenaline signals to neurons causing muscle contraction and phosphorylase kinase activation

Question 4

Describe how neuronal signalling is affected in the FFF response

Answer 4

Neurons release ACh onto ACh receptor
Ca2+ released from ER
Calciul causes muscle contraction
Calcium activates Phosphorylase kinase
Glycogen phosphorylase is activates

Question 5

Describe the steps in the synthesis of Insulin

Answer 5

Preproinsulin

Proinsulin
Signal sequence removed
Disulfide bridges form between A-B and intra chain on A

Insulin
C peptide removed

Question 6

Give an overview of the insulin signal-transduction pathway

Answer 6

1. Insulin binds to the insulin receptor (a tyrosine kinase)
2. Tyrosine kinase phosphorylates IRS-1
3. Phosphorylated IRS-1 activates PI-3K
4. PI-3K catalyses PIP2 -> PIP3
5. PIP3 activates PKB
   6a. PKB upregulates GLUT4 placement in muscle and fat cells
   6b. PKB deactivates GSK3, which can now no longer deactivate Glycogen synthase

Question 7

What is the receptor in the insulin signal-transduction pathway?

What type of receptor is it?

Answer 7

Insulin receptor

Tyrosine kinase

Question 8

Describe what the receptor in the insulin signal-transduction pathway does

Answer 8

It phosphorylates IRS-1

Question 9

What are the targets of PIP3 ? (3)

Answer 9

1. Glycogen synthase
2. GLUT4
3. Glycogen phosphorylase inhibited

Question 10

How is the MAPK pathway implicated in the post Prandial state?

Answer 10

After we have eaten, protein synthesis is upregulated by MAPK

Insulin signals to muscle and liver cells
IRS-1 is activated and activates Grb-2, which then continues on with the MAPK pathway, activating transcription of genes

Question 11

What does PIP3 stand for?

Answer 11

Phosphatidyl inositol tri-phosphate

Question 12

Where are PIP2 and PIP3?

Answer 12

In the cell membrane

Question 13

Describe GLUT4 deposition in muscle and fat cells

Answer 13

Insulin triggers the deposition of GLUT4 in the membrane of muscle and fat cells so that glucose may be taken up from the blood.

PIP3 activates a protein that leads to deposition of GLUT4

Question 14

Wat diseases are associated with insulin?

Answer 14

Diabetes mellitus

Question 15

What is the incidence of diabetes in Australia?

Answer 15

4.3% and rising

Question 16

What are the two types of diabetes?

Answer 16

Type I: autoimmune destruction of B cells that secrete insulin

Type II: prevalent in obese people, may be genetic. Caused by diet as well

Question 17

What are the symptoms of diabetes?

Answer 17

Dizziness
Blackouts
Lethargy

Question 18

What are the biochemical symptoms of diabetes?

Answer 18

Elevated blood glucose during fasting (above 7 mM)

Question 19

How is diabetes treated?

Answer 19

Synthetic insulin post-Prandially in Type I

Change of diet, weight loss and exercise can reverse type II

Question 20

How can diabetes be diagnosed?

Answer 20

Oral tolerance test of glucose

Give a person glucose, and monitor glucose concentration in blood

Normal: 7-8 mM
Impaired glucose tolerance: 8-11
Diabetes: more than 11

Question 21

What type of molecule is insulin

Answer 21

It is a peptide hormone

Question 22

From where is insulin released?

Under what conditions will it be released?

Answer 22

It is synthesised by the beta cells in the pancreas

It is release when there is high blood glucose concentration (above 7 mM)