Biochem - Glucose Management

Question 1

What is the main function of insulin?

Answer 1

To reduce blood glucose levels by promoting target tissues to undergo anabolism and increase glucose storage

Question 2

Why is too much insulin a problem?

Answer 2

The brain cannot produce it’s own glucose so requires blood glucose

Question 3

What determines when beta cells secrete insulin?

Describe the pathway for insulin secretion in a beta cell

Answer 3

Blood glucose levels

Glucose enters cell via GLUT2

Glucolysis = increased ATP

Opens ATP dependant K+ channels

Depolarises cell membrane

Increased Ca2+ influx

Ca2+ causes insulin to be released

Question 4

What are the function of the A chain, B chain and C-peptide?

Answer 4

A + B chain -> form 3D structure which allows insulin to fit in receptors

C-peptide - doesn’t have a function

Question 5

When insulin is bound to C-peptide what is it known as?

Answer 5

Proinsulin

Question 6

What are the unique components of the beta cell that allow it to provide the right amount of insulin at the right time?

Answer 6

Glucokinase’s Km is within 4.5-5.5 and is v responsive to changes in blood sugar levels

Increased blood glucose breakdown is proportional to insulin secretion (look at insulin secretion pathway)

Question 7

What happens to glucose stimulated insulin secretion in T1 and T2 diabetes?

Answer 7

T1 - v v few beta cells left so v little production

T2 - blood glucose is so high that change has v little impact on insulin production - desensitised - always high levels of insulin

Question 8

What mechanisms underpin the biphasic release of insulin and how does this change in T2 diabetes?

Answer 8

1st phase = immediately avaliable insulin from RRP (readily releasable pol)

2nd phase = insulin that has to be prepared before release

T2 diabetes = flattens and weakens due to desensitisation

Question 9

For each of the following types of diabetes what is the pathological cause?
T1
T2
Gestational
Maturity onset diabetes of the young (MODY)
Neonatal

Answer 9

T1 - AUTOIMMUNE destruction of beta cells

T2- insulin insensitivity due to constant high levels

Gestational - diabetes during pregnancy

MODY - destruction of beta cells but NOT autoimmune

Neonatal - mutations in glucose sensor mechanisms

Question 10

What is DKA, how does it occur?

Answer 10

Diabetic ketoacidosis

Increased lipolysis (insulin normally inhibits) - more common in T1

Question 11

Pancreatic islets consist of 3 main cell types what are they and what do they release?

Answer 11

• Alpha = glucagon
• Beta = insulin
• Delta = somatostatin

Question 12

When body goes into hypoglycaemia describe what happens to hormone production in the pancreatic islets?

Answer 12

1. Insulin production stops

2. Glucagon production begins

Question 13

Describe the relationship between insulin secretion and insulin sensitivity in:

• normal population
• T2 diabetic

Answer 13

Increase sensitive, less insulin produced

Normal population - highly variable

T2 - decreased sensitivity and decreased production

Question 14

When the pancreatic islets are analysed in a patient with long standing T2 diabetes, what is a classic sign?

Answer 14

Degranulation - v v little insulin detected in insulin vesicles

Question 15

GLP-1 and GIP are incretins produced in the gut that amplify insulin secretion.

What cells produce them and where are they found?

Answer 15

L cells in distal intestine

Question 16

What is meant by paracrine signalling?

Give an example of it occurring within the pancreatic islets

Answer 16

Cell releasing a substance that induces a reaction in a cell v close to it
e.g. somatostatin binding to alpha/beta cells and inhibiting the function

Question 17

What happens to glucagon in T2 diabetes?

Answer 17

High all the time -> plays a role in continual hyperglycaemia

Question 18

How does glucagon work to increase blood sugar levels?

Answer 18

Induces gluconeogenesis and glycogen catabolism in the liver

Question 19

What is basal insulin levels?

Answer 19

50% of insulin secreted = basal insulin levels

50% = post-prandial = post meals

Question 20

How can T1 and T2 be differentiated on histology?

Answer 20

T1 = insulitis = lymphatic inflitrate 
T2 = amyloidosis (aggregates of protein)

Question 21

How is insulin used?

Answer 21

1x basal long acting insulin

Short acting after every meal based on CHO intake

Question 22

What transplant surgery has recently started to be used in patients with uncontrolled diabetes/incapacitating emotional effects?

Will it make the patient insulin independent?

Answer 22

Pancreatic islet transplant
- easier and better tolerated than full pancreatic transplant

Not always but will stop incapacitating hypos

Question 23

What effect do beta blockers have on insulin release?

Answer 23

Inhibit

Question 24

What effect does somatostain have on insulin when released from pancreas?

Answer 24

Inhibits beta cell release of insulin

Decrease in insulin