Biochemistry of Insulin Production, Secretion and Action Flashcards Preview

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Flashcards in Biochemistry of Insulin Production, Secretion and Action Deck (63)
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1

At what blood glucose level is insulin produced?

Above 5mM

2

At what blood glucose level is glucagon released?

Below 5mM

3

Which cells in the pancreas are responsible for secreting insulin?

Beta cells

4

Which cells in the panreas release glucagon?

Alpha cells

5

What are the basic stages in the synthesis of the insulin hormone?

It is synthesised in the RER of beta cells

First preproinsulin is formed

The C peptide is cleaved from this molecules leaving two polypeptide chains (A and B) linked by disulfide bonds

6

What is the name given to a very fast and short acting insulin preparation?

Lispro

7

What is the name given to an ultra long acting insulin preparation?

Glargine

8

What must Lispro be used in conjunction with for continuous insulin infusion?

A longer-acting insulin preparation

(it is useful for around meals)

9

Using Lispo, has a major disadvantage which is the fact it is antigenic

True or false?

False

It is not antigenic

10

Why is glargine so long lasting?

It precipitates in the subcutaneous tissue

11

How does glucose enter beta cells and what occurs when it does?

GLUT2 transporters

Phosphorylated by glucokinase

12

Why does a change in glucose concentrations above 5mM lead to a dramatic change in glucokinase activity?

The Km for glucokinase is around 5mM of glucose

13

If there is an increased metabolism of glucose within beta cells, there will therefore be  subsequent increase of what in the cell?

ATP

 

14

What is the consequence of a raised intracellular ATP within beta cells?

ATP inhibitis KATP channels

This causes depolarisation

15

When a pancreatic beta cell is depolarised via high intracellular ATP, what is the outcome?

Ca2+ voltage gated channels will open

This causes secretory vesicles to fuse with the cell membrane and release insulin

16

Normally the release of insulin is __________

Normally the release of insulin is biphasic

17

Why are two phases of insulin release usually required?

Only 5% of insulin granules are ready for release at the initial period

The reserve pool must undergo preparatory reactions in order to be ready for release

18

What is the term given to the pool of insulin that is ready for immediate release?

Readily releasable pool

19

Which two proteins does KATP consist of?

  1. KIR - Inward rectifier subunit (Kir6)
  2. Sulphonylurea receptor - Regulatory subunit (SUR1)

20

KATP can be directly inhibited by which class of drugs?

Sulphonylurea

21

Give two examples of drugs within the sulphonylurea drug class

  1. Gliclazide
  2. Glipizide
  3. Glibenclamide
  4. Glimepiride

22

What stimulates KATP and what is the outcome of this?

Diazoxide

Insulin secretion is inhibited

23

Which drug class can be used alongside metformin as an adjunct to first line treatment for type 2 DM?

SURs

24

A mutation in what will lead to neonatal diabetes?

Kir6.2

(this may lead to increased KATP activation or increase in numbers)

25

How can congenital neonatal diabetes be treated?

Sulfonylureas

26

Mutations in which things may lead to congenital hyperinsulinism?

  1. Kir6.2
  2. SUR1

27

Which treatment may help congenital hyperinsulinism?

Diazoxide

28

What is MODY?

Maturity onset diabetes of the young

29

What can cause MODY?

  1. Monogenic diabetes with beta cell genetic defect
  2. Familial form of early onset type II diabetes with defects in insulin secretion
  3. Mutations in at least 6 different genes other genes (there are around 150 genes)

30

What causes MODY2?

Mutations in the glucokinase genes

Impaired glucokinase function