Topic 7.4

Question 1

“type” of molecule that insulin is

Answer 1

antidiabetic / antiketogenic

Question 2

2 steps of insulin synthesis

Answer 2

• pre-pro-insulin
• pro-insulin
• insulin + c peptide

Question 3

How is insulin stored?

Answer 3

complexed with Zn2+ in granules (180 units in pancreas)

Question 4

2 stages of electrical activity of beta cells

Answer 4

• early peak phase

- sustained phase

Question 5

Difference between EPP and SP?

Answer 5

EPP : the readily releasable pool of granules is released, SP has more granules not near the membrane released

Question 6

What does glucose induce? (2)

Answer 6

• Exocytosis of insulin

- Transcription of insulin (if long exposure)

Question 7

What is the incretin effect?

Answer 7

feed forward mechanism that increases insulin secretion

Question 8

Which molecules contribute to incretin effect?

Answer 8

• GLP and GIP (enterohormones)

Question 9

What do GLP and GIP bind to?

Answer 9

Gs coupled receptor

Question 10

Which molecules can decrease glucagon secretion?

Answer 10

GLP-1

Question 11

7 activators of insulin secretion

Answer 11

1. Glucose
2. AA (K, R, L)
3. Enterohormones (GLP, GIP)
4. Glucagon
5. B adrenergic R
   6 Vagus stimulation via M1R
6. FFA

Question 12

4 inactivators of insulin secretion

Answer 12

1. Hypoglycaemia
2. SST
3. Leptin
4. Alpha2R
   (Gi receptors)

Question 13

Where can we find K-ATP

Answer 13

• beta cells of pancreas
• in SA node
• in vascular smooth muscle

Question 14

What is K-ATP?

Answer 14

ATP regulated K+ channel

Question 15

7 steps of release of insulin by beta cells

Answer 15

1. Glucose enters through glut2
2. Glycolysis
3. ATP inhibits K-ATPase : K+ trapped in
4. Depolarization
5. VDCC open
6. Release of insulin granules
7. VDK+ channels drive repolarization

Question 16

Pharmacological inhibition of insulin secretion

Answer 16

diazoxid

Question 17

Pharmacological stimulation of insulin secretion

Answer 17

sulphonyl urea (binds to K-ATP SU)

Question 18

What does the insulin receptor recruit after autophosphorylation?

Answer 18

IRS-1

Question 19

What 2 pathways can IRS1 activate?

Answer 19

• MAP kinase pathway

- PI3K pathway

Question 20

What does the map kinase pathway result in?

Answer 20

mitogenic signals

Question 21

What does PI3K pathway result in?

Answer 21

activation of PKB and PKC

Question 22

What do PKB and PKC do?

Answer 22

phosphorylate rab4

Question 23

What does rab4 do? (2)

Answer 23

• release GLUT4 vesicles

- increase glycolysis

Question 24

Effect of insulin on intermediary metabolism in liver (4)

Answer 24

• increase glycolysis
• increase glycogenesis
• decrease glycogenolysis
• decrease gluconeogenesis

Question 25

Effect of insulin on skeletal muscle IM (4)

Answer 25

- increase glycolysis - increase protein anabolic effect - increase glycogenesis - decrease FFA and ketone bodies use

Question 26

Effect of insulin on adipose tissue (3)

Answer 26

- clears lipids from plasma - lipoprotein lipase increases breakdown of FFA - decreases breakdown of TG

Question 27

Overall anabolic effect of insulin (4)

Answer 27

- increase protein synthesis - increase lipogenesis - increase glycogenesis - decrease gluconeogenesis

Question 28

2 types of diabetes

Answer 28

type 1 : insulin dependant | type 2 : insulin independant

Question 29

What is type 1 diabetes due to?

Answer 29

autoimmune destruction of beta cells

Question 30

3 effects of type 1 diabets

Answer 30

- excessive glucose : osmotic diuresis | - ketone bodies : ketoacidosis, vomiting

Question 31

What is type 2 diabetes due to?

Answer 31

- limitation of ability to produce enough insulin | - resistance to insulin

Question 32

Treatment of type 2 diabetes?

Answer 32

- change diet - exercise (glut4) - sulfonylurea - TZD (tiazolidin-dion drugs)

Question 33

What does TZD do?

Answer 33

- decrease resistin secretion | - increase adiponectin secretion (decrease resistance)

Question 34

3 diagnostic tests for diabetes

Answer 34

1. Glucose tolerance test (fasting and 2 hours after ingesting glucose) 2. Glycated Hb 3. C peptide