Insulin

Question 1

Outline the structure of insulin

Answer 1

• Made up of two polypeptide chains joined by 2 disulfide bridges
• 1 internal disulfide bridge on the α chain

Question 2

Outline the formation of mature insulin

Answer 2

• Preproinsulin produced in RER
• Signal sequence is cleaved in the golgi to produce proinsulin
• Prosinsulin cleaves off the C peptide by proteases to produce mature insulin

Question 3

Where is insulin secreted from?

Answer 3

Insulin is secreted from β cells in the pancreas

Question 4

Outline secretion of insulin

Answer 4

• Biphasic
• First a release of preformed insulin
• Synthesis and release of new insulin

Question 5

What hormone can inhibit insulin secretion?

Answer 5

Adrenaline

Question 6

What factors stimulate insulin secretion?

Answer 6

• Amino acids
• Fatty acids

Question 7

Through what transporter does glucose enter β cells?

Answer 7

GLUT2

Question 8

What is the advantage of the GLUT2 transporter having a low affinity for glucose?

Answer 8

So β cells don’t take up as much glucose when [glucose] is low

Question 9

How many subunits is the insulin receptor made up of?

Answer 9

4

Question 10

What is stimulated when insulin binds to the insulin receptor?

Answer 10

Intrinsic tyrosine kinase activity of β subunits

Question 11

What molecule is an important mediator in insulin signalling?

Answer 11

PIP3

Question 12

What reverses phosphorylation of PIP3?

Answer 12

PTEN

Question 13

What is the other role of PTEN?

Answer 13

An important tumour receptor

Question 14

Where are GLUT4 transporters found?

Answer 14

Specifically in muscle and adipose tissue

Question 15

How does insulin stimuate glucose uptake in muscle and adipose tissue?

Answer 15

Insulin stimulates movement of vesicles to plasma membrane and delivers GLUT4 transporters to the cell surface so glucose can be moved into the cell

Question 16

What are the 3 ways of diagnosis of diabetes?

Answer 16

1. Oral glucose tolerance test
2. Measurement of Plasma Insulin Levels
3. Urine analysis

Question 17

What is the renal threshold?

Answer 17

The [blood glucose] above which glucose can be detected in the urine

Question 18

How is an oral glucose tolerance test completed?

Answer 18

• Patient is given a drink contaning a known high [glucose]
• Blood glucose is measured ar regular intervals

Question 19

How are plasma insulin levels tested?

Answer 19

• Competition radioimmunoassays or
• ELISA

Question 20

Whys is measurement of plasma insulin levels useful?

Question 21

What is the effect of decreased insulin/glucagon ratio on triglyceride metabolism?

Answer 21

• Increased lipolysis
• Increased fatty acid oxidation
• Increased ketone body formation

Question 22

How can diabetes be monitored?

Answer 22

• Glucose meter
• Measurement of glycosylated Hb

Question 23

What is measurement of glycosylated Hb also a measurement of?

Answer 23

Hyperglycaemia

Question 24

What are the effects of a decreased insulin/glucagon ratio on carbohydrate metabolism?

Answer 24

• decreased gluose uptake by muscle and adipose
• Increased glycogen breakdown
• Increased gluconeogenesis

Question 25

Does the liver contain GLUT 4 receptors?

Answer 25

No

Question 26

What are the 3 types of drugs used to treat diabetes?

Answer 26

• Thiazolidinediones
• Biguanides
• Sulphonylureas

Question 27

What is used to treat diabetes?

Answer 27

• Insulin
• Diet
• Drugs

Question 28

What do Thiazolidinediones do?

Answer 28

Increase insulin sensitvity

Question 29

What do biguanides do?

Answer 29

Increase glucose uptake in peripheral tissues and decrease gluconeogenesis

Question 30

What do sulphonylureas do?

Answer 30

Inhibit ATP-gated K+ channels so increase insulin secretion