Insulin Production And Action

Question 1

What does preproinsulin lose to became proinsulin?

Answer 1

It’s signal sequence.

Question 2

What does proinsulin lose to become insulin?

Answer 2

It’s C-chain

Question 3

What two chains make up an insulin molecule?

Answer 3

A and B chains, connected via sulphide bridges.

Question 4

Glucagon and what other hormones are produced from the precursor molecule mammalian preproglucagon?

Answer 4

Oxyntomodulin
GRPP
IP-1 and 2
GLP-1 and 2
Glicentin
MPGF

Question 5

Which hormones derived from mammalian preproglucagon are secreted from the pancreas?

Answer 5

Glucagon

MPGF

Question 6

Which hormones derived from mammalian preproglucagon are secreted from the brain and GI tract?

Answer 6

Glicentin
Oxyntomodulin
GLP-1 and 2
IP-2

Question 7

How is glucose enters into beta-cells mediated?

Answer 7

GLUT-2 facilitated transporters

Question 8

Which two ion channels control insulin release from beta cells?

Answer 8

ATP sensitive potassium channels -normally open and allowing potassium to leave the cell
Voltage-gated sodium channels - normally closed, not allowing sodium into the cell

Question 9

How does insulin secretion occur?

Answer 9

Glucose enters the cell, undergoes glycolysis and produces lots of ATP
The ATP sensitive potassium channels, detect the increase in ATP and close
This allows potassium to build up within the cell, causing depolarisation
When the potassium concentration in a cell reaches a certain level, the calcium channels open
Calcium diffuses down the concentration gradient, into the cell, causing vesicles containing insulin to be exocytosed

Question 10

What is known about glucagon secretion?

Answer 10

Not much, just that its released in response to low glucose concentrations

Question 11

Where are insulin receptors normally found?

Answer 11

Liver, striated muscle and adipocytes

Question 12

What signalling cascade is initiated when insulin binds to the tyrosine kinase receptor on the cell surface?

Answer 12

IRS - insulin receptor substrate

This then activates PI3K, which in turn activates protein kinase B.

Question 13

What actions does protein kinase B have on striated muscle, adipocytes and the liver?

Answer 13

Liver - gluconeogensies inhibition
- glycogen synthesis stimulation
- fatty acid synthesis stimulation
Muscle - glycogen synthesis stimulation
- glucose transport stimulation
Adipocytes - lipolysis inhibition
- FA synthesis stimulation
- glucose transport stimulation

Question 14

What receptor does glucagon bind to and where is it found?

Answer 14

It binds to a G-protein coupled receptor and is found in hepatocytes

Question 15

What happens inside the cell when glucagon binds to a G-protein coupled receptor?

Answer 15

GTP activates a G-protein, which in turn activates the enzyme adenylyl cyclase.
This uses ATP to activate cAMP (the second messenger), which activates protein kinase A, which has the affect on the cell.

Question 16

What does insulin have a stimulatory effect on (cellularly, not enzymatically)

Answer 16

Glycogen storage in the liver and muscles
Glucose uptake by tissues (muscle and adipocytes)
Synthesis of FAs and triglycerides

Question 17

What does glycogen have a stimulatory effect on (on a cellular, not enzyme level)?

Answer 17

Glycogen breakdown from the liver

Gluconeogensis by the liver

Question 18

What stimulatory effects does insulin have on adipose tissue in the fed state?

Answer 18

It stimulates glucose transport into the cel, via the GLUT-4 receptor
It stimulates the action of acetyl CoA carboxylase (ACC) - converting acetyl-CoA to malonyl CoA
It stimulates lipoprotein lipase, so the LDLs release more FAs into the tissue

Question 19

What inhibitory action does insulin have on adipocytes in the fed state?

Answer 19

The protein kinase B inhibits lipolysis by the inhibiting cAMP secondary messenger produced by glucagon binding to its GPCR.

Question 20

How does glucagon stimulate lipolysis in the fasted state?

Answer 20

It binds to its GPCR, which activates the secondary messenger cAMP, which activates PKA.
PKA has a stimulatory effect on hormone sensitive lipase, so breaking down triglycerides.

Question 21

What is the thing that kickstarts the switch from using fat sisters to using glucose just being taken into the body?

Answer 21

Insulin binds to its tyrosine kinase receptor on adipocytes, inhibiting lipolysis.
This causes the FA concentration to decrease.
Reduction in FA concentration is what causes the muscles to switch to oxidising glucose

Question 22

What are the three main cells in the islets of langerhans and what do they secrete?

Answer 22

Alpha cells - secrete glucagon
Beta cells - secrete insulin
Delta cells - secrete somatostatin