Introduction to Diabetes Mellitus: Insulin Action

Question 1

In which tissues is Glut-4 usually found?

Answer 1

Most glucose uptake is via Glut-4

It is particularly abundant in MUSCLE and ADIPOSE tissue

Question 2

How is Glut-4 different to Glut-2?

Answer 2

Glut-4 is insulin responsive whereas Glut-2 isn’t

Question 3

How does insulin affect proteolysis?

Answer 3

Inhibits proteolysis

Question 4

How does cortisol affect proteolysis?

Answer 4

Promotes proteolysis (cortisol is a stress hormone that is concerned about increasing blood glucose)

Question 5

What effect does glucagon have on uptake of amino acids by the liver?

Answer 5

Increases uptake of amino acids by the liver

Question 6

What do gluconeogenesis and glycogenolysis in the liver contribute towards?

Answer 6

Hepatic Glucose Output

Question 7

How do triglycerides enter adipocytes?

Answer 7

Triglycerides must be broken down by LIPOPROTEIN LIPASE before they can enter the adipocyte.
Triglycerides are broken down by lipoprotein lipase to:
Glycerol
Non-Esterified Fatty Acids (NEFA)

Question 8

How is glucose converted to triglycerides?

Answer 8

Glucose can be converted to NEFA
Glucose can also be chopped in half to produce glycerol
They can then be stuck together to make triglycerides

Question 9

How are the effects of insulin in the blood different to insulin in adipocytes?

Answer 9

Blood - insulin promotes the breakdown of triglycerides (so that they can enter the adipocytes)
Adipocytes - insulin promotes the formation of triglycerides so that they can be stored

Question 10

What are the two ways in which glycerol can be used by the liver?

Answer 10

Glycerol can be used to make TRIGLYCERIDES for storage

Glycerol can be used to make GLUCOSE that supports hepatic glucose output

Question 11

What are the three main ketone bodies?

Answer 11

Acetone
Acetoacetate
3-hydroxybutyrate

Question 12

What are the effects of insulin and glucagon on fatty acid metabolism?

Answer 12

Insulin inhibits the conversion of fatty acids to ketone bodies
Glucagon promotes the conversion of fatty acids to ketone bodies

Question 13

What does a high blood glucose and high ketone bodies indicate?

Answer 13

Insulin Deficient
Explanation: Insulin promotes uptake of glucose from the blood and inhibits conversion of fatty acids to ketone bodies
So…
High blood glucose and high ketone bodies must mean that they are INSULIN DEFICIENT

Question 14

When are ketone bodies produced?

Answer 14

Produced at times of LOW FOOD INTAKE or CARBOHYDRATE RESTRICTION

Question 15

How do insulin, catecholamines and glucagon affect glycogenolysis?

Answer 15

Insulin - promotes STORAGE of glucose as glycogen

Catecholaines and Glucagon - promote the break down of glycogen to produce glucose (promote glycogenolysis)

Question 16

What effect do stress hormones have on the uptake of glucose by muscle cells?

Answer 16

Stress hormones inhibit the uptake of glucose via Glut-4 (because it is trying to increase blood glucose so one way of doing this is by decreasing uptake)

Question 17

What is the usual presentation of Type 1 Diabetes Mellitus?

Answer 17

Polyuria
Polydipsia
Nocturia
Proteolysis with weight loss 
Ketonuria

Question 18

What is used as a treatment for insulin induced hypoglycaemia?

Answer 18

Intramuscular glucagon

Question 19

Where does insulin resistance lie?

Answer 19

Liver, muscle and adipose tissue

It is not a problem with the insulin or the receptor but instead a problem with the post-receptor pathways

Question 20

How can you differentiate between T1DM and T2DM?

Answer 20

REMEMBER: insulin inhibits the conversion of fatty acids to ketone bodies
HIGH glucose + HIGH ketone bodies = T1DM
Usually, people with T2DM still produce enough insulin to suppress ketone body production though their blood glucose will be high.

Question 21

What two pathways does insulin have an effect on?

Answer 21

Metabolic Pathway (PI3K-Akt)
Mitogenic Pathway (MAPK)

Question 22

What is the significance of having two pathways in someone who has insulin resistance?

Answer 22

The feedback loop for insulin is mainly through blood glucose concentration
Someone with some degree of insulin resistance will have produce a compensatory hyperinsulinaemia so that they make enough glucose to maintain normal blood glucose
But this high insulin will still be harming them because it has an INCREASE EFFECT ON THE MITOGENIC (MAPK) PATHWAY

Question 23

State some characteristic features of insulin resistance.

Answer 23

Hypertension
High LDL
Low HDL
Raised fasting blood glucose 
High omental fat (more than 6mmol/l)
Adipocytokines

Question 24

What does omental fat/waist circumference indicate?

Answer 24

an individual’s risk of ischaemic heart disease

Question 25

What can and can’t the brain metabolise?

Answer 25

glucose, ketone bodies and fatty acids

Question 26

Hoe does insulin and glucagon affect the conversion of fatty acyl CoA to ketone bodies?

Answer 26

Insulin inhibits conversion of fatty acyl coA –> ketone bodies
Glucagon promotes conversion of fatty cayl coA –> ketone bodies

Question 27

Define ketone bodies

Answer 27

3 water-soluble molecules that are produced by the liver from fatty acids during periods of low food intake or carbohydrate restriction.

Question 28

What happens when you fast?

Answer 28

Increase:
Conc of NEFA
Proteolysis
Lipolysis 
HGO ( due to glycogenolysis and gluconeogenesis) 
Decrease:
Amino acid conc ( when prolonged)

Question 29

What happens in the fed state?

Answer 29

Increase:
Glycogen
Protein synthesis 
Lipogenesis
Decrease:
Proteolysis 
Gluconeogenesis

Question 30

What happens during insulin-induced hypoglycaemia?

Answer 30

Increase:
insulin 
glucagon
catecholamines
cortisol 
somatotrophin 
Decrease: 
HGO 
Lipolysis

Question 31

What’s the usual presentation of T2DM?

Answer 31

60-80% obese
Dyslipidaemia
Later insulin deficiency ( exhaustion of beta cells )
hyperglycaemia
fewer osmotic symptoms
T2DM presents often with complications