Biochemistry of Insulin

Question 1

Which cells secrete insulin?

Answer 1

b-cells

Question 2

Which cells secrete glucagon?

Answer 2

alpha cells

Question 3

Which cells secrete somatostatin?

Answer 3

d cells

Question 4

Which cells secrete pancreatic polypeptide?

Answer 4

PP cells

Question 5

Where is insulin made?

Answer 5

RER in b cells of pancreas

Question 6

What is insulin synthesized as?

Answer 6

larger single chain preprohormone called preproinsulin

Question 7

What chains does insulin contain?

Answer 7

2 polypeptide chains, linked by disulphide bonds

Question 8

Why is human insulin now used?

Answer 8

to avoid problem of antibody formation

Question 9

What is the glucose sensor which leads to insulin secretion?

Answer 9

Glucokinase

Question 10

How does glucose enter b cells?

Answer 10

through GLUT2 glucose transporter

Question 11

What phosphorylyses glucose?

Answer 11

glucokinase

Question 12

What does a change in glucose concentration lead to?

Answer 12

dramatic change in glucokinase activity

Question 13

Increased metabolism of glucose leads to what happening to intracellular ATP?

Answer 13

increases

Question 14

What does ATP do to the KATP channel?

Answer 14

inhibits this

Question 15

What does inhibition of KATP lead to?

Answer 15

depolarisation of cell membrane

Question 16

What does depolarisation of cell membrane result in opening of?

Answer 16

calcium channels

Question 17

How does an increases in calcium concentration in the cells cause insulin release?

Answer 17

leads to fusion of secretory vesicles

Question 18

What is release of insulin in terms of phases?

Answer 18

biphasic

Question 19

Why are there two phases of insulin?

Answer 19

5% of insulin granules immediately ready for release

Reserve pool must undergo preparatory reactions to become mobilised and available for release

Question 20

Which proteins do KATP channels consist of?

Answer 20

KIR6.1 (inward rectifier subunit, pore)

SUR1 (sulphonylurea receptor, regulatory)

Question 21

What type of structure is the KATP channel

Answer 21

octomeric

Question 22

Are both proteins (KIR6.1 and SUR1) required for a functional channel to form?

Answer 22

YES BOTH

Question 23

Which class of drugs directly inhibits KATP?

Answer 23

sulphonylureas eg glibenclamide, tolbutamide

Question 24

What is KATP stimulated by?

Answer 24

diazoxide

Question 25

What does diazoxide do to insulin secretion?

Answer 25

inhibits

Question 26

What causes MODY?

Answer 26

mutations - genetic defect in b cell function

Question 27

What type of diabetes is MODY?

Answer 27

familial version of Type II

Question 28

What do HNF transcription factors and MODY play a key role in?

Answer 28

pancreas foetal development and neogenesis | regulate beta cell differentiation and function

Question 29

What allows for differentiation between type 1 diabetes and MODY?

Answer 29

robust genetic screening - means MODY can be treated with sulphonylurea rather than insulin

Question 30

loss of insulin secreting beta cells?

Answer 30

type 1 diabetes

Question 31

defective glucose sensing in the pancreas and/or loss of insulin secretion?

Answer 31

MODY

Question 32

Initially hyperglycaemia, with hyperinsulinaemia, so primary problem is reduced sensitivity in tissues?

Answer 32

Type 2 diabetes

Question 33

What type of receptor are insulin receptrs?

Answer 33

receptor kinases

Question 34

What provides for a reversible method for altering protein function?

Answer 34

protein phosphorylation

Question 35

What can proteins get phosphorylated onto?

Answer 35

any hydroxyl group, introduces large negative charge into protein structure

Question 36

What is the insulin receptor?

Answer 36

a dimeric tyrosine kinase

Question 37

Name a rare autosomal recessive genetic trait with mutations in the gene for insulin receptor causing growth retardation, decreased muscle mat, no subcutaneous fat and elfin facial appearance?

Answer 37

leprechaunism/Donohue syndrome

Question 38

Which autosoma recessive trait causes severe insulin resistance, hyper glycaemia, developmental abnormalities and acanthosis nicrigans?

Answer 38

rabson mendenhall syndrome

Question 39

Where are ketone bodies formed?

Answer 39

liver mitochondria

Question 40

What organs are ketone bodies important molecules of energy for?

Answer 40

heart muscle | renal cortex

Question 41

What does fatty acid oxidation yield?

Answer 41

acetyl CoA

Question 42

What can accumulation of ketone bodies lead to?

Answer 42

acidosis

Question 43

What type of diabetes is ketoacidosis associated with?

Answer 43

type 1