Week 1/2 - A - Biochemistry of insulin

Question 1

Which hormone promotes the conversion of glucose to glycogen? Where is glucagon stored?

Answer 1

Insulin promotes the conversion of glucose to glycogen

Glucagon is stored in the liver, skeletal tissue and adipose tissue

Question 2

What is the normal range for blood glucose?

Answer 2

Normal range is between 4 and 6

Question 3

What cells of the pancreas are the endocrine pancreas? Which cells are the exocrine part of the pancreas?

Answer 3

Islets of langerhans - endocrine pancreas

Acinar cells - exocrine pancreas

Question 4

What are the 4 cells of the endocrine pancreas and what do they secrete?

Answer 4

a cells - secrete glucagon

b cells - secrete insulin

delta (fancy S) cells - secrete somatostatin

PP cells - secrete pancreatic polypeptide

Question 5

Which of the 4 pancreatic cells is the most abundant?

Answer 5

The beta cells secreting insulin

Question 6

Where in the pancreatic B cells is insulin synthesised?

Answer 6

In the rough endoplasmic reticulum

Question 7

Insulin is synthesised as a preprohormone in the rough ER of the beta cells, what is the name of this? What is preproinsulin cleaved to form?

Answer 7

Preproinsulin

Cleaved to form proinsulin + signal peptide

Question 8

What is proinsulin cleaved to form?

Answer 8

Cleaved to form insulin and C-peptide in a one to one ratio

Question 9

Insulin contains two polypeptide chains linked by what type of bonds?

Answer 9

Disulphide bonds

Question 10

What chemical can often be used to measure the endogenous insulin levels? This can be done so though exogenous insulin, does not interfere with the insulin reading

Answer 10

Measure the C-peptide levels as they are form in a one to one ratio with endogenous insulin production

Question 11

When glucose enters the pancreatic B cells, what transporter takes up the glucose?

Answer 11

GLUT2 - glucose transporter 2

Question 12

When glucose is taken up by the GLUT 2 transporter, what is the enzyme that phosphorylates glucose to glucose-6-phosphate to make glucose ready for the process of respiration?

Answer 12

Glucokinase or hexokinase phosphorylates the glucose

Question 13

Does glucokinase or hexokinase have a greater affinity for glucose?

Answer 13

Hexokinase has a greater affinity

Glucokinase only works at high glucose concentrations however has a greater Vmax

Question 14

Once glucose enters the respiratory cycle, what does this increase the intracellular concentration of and what effect does this have?

Answer 14

Produces ATP which inhibits the ATP sensitive potassium channels

Question 15

How does the inhibition of the ATP sensitive potassium channels lead to the release of glucose? (what fuses with cell membrane)

Answer 15

This leads to depolarization of the cell membrane causing the influx of calcium via the voltage gated calcium channels

The intracellular increase in Calcium concentration causing the fusion of secretory vesicles with the cell membrane and release of insulin

Question 16

What two proteins does the Katp channel consist of?

Answer 16

An inward rectifier potassium subunit (Kir) - pore subunit – Kir6

A sulphonylurea receptor - regulatory subunit - SUR1

Question 17

What type of structure does the Katp channel exist as?

Answer 17

It exists as an octomeric structure

(4xSUR & 4xKIR)

Question 18

What effect does the sulphonylurea class of drugs have on the K_ATP channel?

Answer 18

K_ATP is directly inhibited by the sulphonylurea class of drugs, e.g. tolbutamide or glibenclamide

Question 19

What class of drugs can inhibit insulin secretion by stimulating the Katp channels of the beta cells?

Answer 19

The diazoxides

Question 20

What can cause congenital hyperinsulinaemia? What class of drugs can help here?

Answer 20

Mutations in the SUR1 subunit or the Kir6.2 subunits can cause this

Diazoxides can help decrease the insulin secretion

Question 21

How does insulin control its own action of release via the negative feedback loop?

Answer 21

The secretion of insulin will lower the plasma glucose conecentration causing less glucose to enter the Bcells and therefore less secretion of insulin will occur

Question 22

Insulin is important in controlling the storage of carbohydrates as a way of reducing blood glucose, How does it stimulate the uptake of glucose into cells? (what transporter)

Answer 22

Facilitates glucose transport into cells via glucose transporter 4 (GLUT4)

Question 23

What are the other 3 ways in which insulin decreases plasma glucose concentration?

Answer 23

Stimulates glycogenesis (synthesis of glycogen from glucose)

Inhibits glycogenolysis (stops breakdown of glycogen into glucose)

Inhibits gluconeogenesis (stops the synthesis of glucose from non-carbohydrate precursors)

Question 24

What is the insulin receptor?

Answer 24

Tyrosine kinase receptor

Question 25

The insulin receptor is a dimeric tyrosine kinase What are the two subunits? What unit does insulin bind to? WHat links the two subunits?

Answer 25

Has two extracellular alpha subunits with insulin binding sites

Has two transmembrane beta subunits

The subunits are linked 4 disulphide bonds

Question 26

What does the binding of insulin to the alpha subunit of the tyrosine kinase receptors cause?

Answer 26

causes the b subunits to phosphorylate themselves - autophosphorylation

Question 27

Once the b subunits autophosphrylates itself, Insulin receptor substrates are phosphorylated Which pathway does this activate for glycogen synthesis?

Answer 27

IRS activate PI3K pathway for glycogen synthesis

Question 28

What does PKB in the P13K pathway stimulate?

Answer 28

Stimulates GLUT4 translocation leading to the uptake of glucose by the cell - causes cell growth

Question 29

when insulin not injected, cells fail to receive enough glucose and switch to fat breakdown What does this lead to a build up of and what condition can it cause?

Answer 29

Leads to a build up of ketones (by product of fat breakdown)

Leads to a condiiton called diabetic ketoacidosis

Question 30

Is diabetic ketoacidosis normally associate with type 1 or type II diabetes?

Answer 30

Normally associated with type 1