18/5 Insulin

Question 1

When insulin is being made its synthesised as?

Answer 1

Proinsulin

Question 2

What class of drug is insulin?

Answer 2

Polypeptide hormone

Question 3

Explain the process of insulin secretion

Answer 3

Rise in blood glucose (5-6mM) detected by GLUT2 in beta cell
-rise in ATP
- inhibits k+ ATP channel
- depolarisation of cell membrane
- activates ca2+ influx into cell
- stimulates insulin secretion & synthesis
- insulin containing granules released

Question 4

Role of insulin:
Glycogenesis
Gluconeogenesis
Glycolysis
Lipolysis
Lipogenesis
Amino acids

Answer 4

Glycogenesis- increases glycogen production in muscle and liver
Gluconeogenesis - decreases glucose production in liver
Glycolysis - increase ATP production in liver and adipose tissue
Decreases lipolysis
Increases lipogenesis and esterification of fatty acids in liver and adipose tissue
Decreases breakdown of amino acid in liver and increases uptake & protein synthesis in muscle, liver and adipose tissues

Question 5

Normal blood glucose

Answer 5

5-6 mmol

Question 6

Lack of secretion of insulin- what type of diabetes ?

Answer 6

Type 1 diabetes

Question 7

Loss of responsiveness to insulin - insulin resistance. What type of diabetes?

Answer 7

Type 2 diabetes

Question 8

How does cow and pig insulin vary from human insulin?

Answer 8

Pig- varies by a single amino acid
Cow- varies by 3 amino acids

Question 9

How can you change the ADME characteristics of insulin?

Answer 9

Altering the amino acid sequence of insulin

Question 10

List 2 insulin replacements

Answer 10

1. Rapid acting insulins (bolus insulins)
2. Long acting insulins ( background insulins)

Question 11

Define lispro

Answer 11

Lysine and proline residues reversed on the C terminal end of the beta-chain

Question 12

Define aspart

Answer 12

Substitution of a proline for aspartic acid

Question 13

When are bolas insulin used?

Answer 13

For injection after eating (post prandial) or in pumps

Question 14

Role of bolus insulins

Answer 14

Lispro + aspart: prevent the formation of insulin dimers= more effective at stimulating the receptor

Question 15

Background insulins have undergone various modification to?

Answer 15

• precipitate in the subcutaneous tissue allowing for slow release
• increase affinity for serum albumins which extend their life span in serum

Question 16

List examples of background insulin

Answer 16

Degludec
LY2605541 and Lantus
Detemir

Question 17

Advantages of long acting insulin

Answer 17

Active in the body for more man 24 hours so patients can maintain good blood sugar
Effective for basal insulin therapy for T1 + T2 diabetes
Reduced hypoglycaemia during the night and reduced severe hypoglycolemia

Question 18

Disadvantages of background insulin

Answer 18

Can cause hypoglycaemia in up to 40% of patients
Some people exhibit allergic reactions

Question 19

Insulin secretagogues are usuallyprescribed for what type of diabetes? And why?

Answer 19

Type 2
Need active pancreative beta cells, T1 diabetes don’t have active beta cells

Question 20

Secretagogues stimulate release of?

Answer 20

Insulin from beta cells

Question 21

2 classes of insulin secretagogues

Answer 21

Sulphonylureas and meglitinide

Question 22

Examples of meglitinides

Answer 22

Repaglinide
Nateglinide

Question 23

Examples of sulfonylureas

Answer 23

1st gen: chlorpropamide
2nd generation: more potent
Glimepiride
Glipizide
Glyburide

Question 24

How do sulphonylureas work?

Answer 24

Stimulate release of insulin
-Act on the sulphonylurea receptor (SUR)
Binding closes linked ATP sensitiveK+ channels
Use k+ infux=depolarisation of beta cell membrane
Ca 2+ channels open= influx of Ca2+
Translocation + exocytosis of secretary granules of insulin

Question 25

How do glinides differ from sulphonylureas?

Answer 25

Similar route of action, rapid onset $ short duration of action but have:

• weaker binding affinity
• faster dissociated from the SUR1 binding site

Question 26

Advantages of insulin secretagogues

Answer 26

Oral tablet form
Flexible but multiple dosing (before meals)
Nateguinide and repaglinide not widely prescribed but provide alternative to a sulfonylurea for people with erratic lifestyles or irregular meal patterns (shift workers)

Question 27

Example of glinides

Answer 27

Meglitinide
Repaglinide (prandin)
Nateglinide (starlix)