Endo 4 - Insulin action

Question 1

What is GLUT-4? Where is it found?

Answer 1

GLUT-4 is an insulin responsive glucose transporter. It is particularly abundant in adipose and muscle
Most glucose uptake is via glut4
7x increase glucose uptake
Glut2 is different as it is not insulin sensitive

Question 2

What are the metabolic effects of insulin?

Answer 2

Decrease HGO
Increase muscle uptake
Decrease proteolysis
Decrease lipolysis
Decrease ketogenesis

Question 3

How does insulin affect proteolysis? lipolysis? ketogenesis? HGO? muscle uptake?

Answer 3

Decrease HGO
Increase muscle uptake
Decrease proteolysis
Decrease lipolysis
Decrease ketogenesis

Question 4

What are the mitogenic effects of insulin?

Answer 4

Growth
Vascular effects - smooth muscle hypertrophy
Ovarian function
CLotting
Energy expenditure

Question 5

How does cortisol affect proteolysis?

Answer 5

promotes proteolysis

Question 6

Describe the protein metabolism

Answer 6

20% of energy expenditure
Insulin inhibits proteolysis whereas cortisol does the opposite
Insulin, GH and IGF-1 stimulate Protein Synthesis (from amino acids)
Insulin also inhibits the conversion of Oxygen to carbon dioxide which is used to osxidise aa
This happes in muscle cell

Question 7

What is HGO?

Answer 7

Glucose that enters the circulation from synthesis in the liver

Question 8

What do insulin and glucagon do in the context of hepatic glycogenolysis?

Answer 8

Glucose enters the liver cell, gets converted to G6P
Effects of Insulin:
Stimulates glycogenesis (the conversion of glucose (more likeG6P) to glycogen).
Inhibits gluconeogenesis (the conversion of glycogen to glucose).
Inhibits hepatic glucose output (the release of glucose from the hepatocytes

Effects of Glucagon:
Stimulates glycogenolysis and gluconeogenesis
Increases hepatic glucose output

Question 9

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

Answer 9

It increases the uptake of gluconeogenic aa

In regards to what happens to these aa in the liver cell:
Insulin promotes protein synthesis, glucagon does the opposite and wants these aa to be used to make glucose to contribute towards HGO (which insulin does not want)

Question 10

What are the energy stores? which are short and long term?

Answer 10

Carbohydrate –> short term

Fat –> long term

Question 11

Into what are triglycerides coming from a meal broken down into? By what?

Answer 11

They are broken down into Glycerol and NEFA to be taken up into the cell (NEFA in cell). This is promoted by lipoprotein lipase and insulin. Then insulin promotes the formation of energy stores - triglycerides- with glycerol + NEFA. Glycerol comes from Glucose which has entered the cell and was converted to glycerol3P
These energy stores can then be used up - promotes by Cathecolamines, cortisol, GH
This is inhibited by insulin (insulin does the opposite - make triglycerides)

Question 12

How is glucose converted in triglycerides?

Answer 12

It can be converted to NEFA
It can also produce glycerol
Glycerol + NEFA does triglyceride

Question 13

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

Answer 13

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 14

What are the 3 main ketone bodies?

Answer 14

Acetone
Acetoacetate
3-hydroxybutyrate

Question 15

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

Answer 15

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

Question 16

What can the liver do to glycerol?

Answer 16

When taken into liver cells, glycerol can be converted to glucose to support HGO
It can also be used to form triglycerides

Question 17

What can the liver do to fatty acids?

Answer 17

Taken up in liver as NEFA
They are converted to Fatty acyl CoA
This is then converted to the ketone bodies which can be used by the brain as an alternate source of energy
Insulin inhibits this process, glucagon promotes it

Question 18

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

Answer 18

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 19

When are ketone bodies produced?

Answer 19

Produced at times of LOW FOOD INTAKE or CARBOHYDRATE RESTRICTION

Question 20

What are the two pathways of insulin?

Answer 20

The MAPK pathway is responsible for growth and proliferation.
The PI3K-Akt pathway is responsible for the metabolic effects of insulin.

Question 21

What is the key difference between glucose storage in adipose and liver cells?

Answer 21

Muscle cells are incapable of liberating glucose in the circulation. It can only be used in muscle cells

Question 22

What happens in the fasted state?

Answer 22

Insulin is inhibited, glucagon is stimulated.
There is a low Insulin: Glucagon ratio.
Blood glucose is maintained between 3.5-5 mM (this is a relatively-fixed range, controlled by circulating hormones).

The low insulin level leads to increased lipolysis. This leads to increased production of NEFA.
There is also a decrease in amino acids in the blood, when prolonged (gluconeogenesis).

Prolonged Fasting:
Proteolysis: Protein is broken down so that amino acids can be used in gluconeogenesis.
Lipolysis: Adipocytes release glycerol and NEFA.
Increased HGO: From gluconeogenesis and glycogenolysis.
Muscles will start using lipids for energy (to conserve glucose)
The brain will use glucose, then ketone bodies.
Ketogenesis: This is the formatin of ketones. It will increase as the insulin levels get very low after prolonged fasting.

Question 23

What happens in the fed state?

Answer 23

Insulin is stimulated, glucagon is inhibited.
There is a high Insulin: Glucagon ratio.
Blood glucose is maintained in the physiological range, by the circulating insulin.

1st Phase insulin –pre-formed insulin is released.
2nd Phase insulin –newly-synthesized insulin is slowly released.

Proteolysis is inhibited, and protein synthesis is stimulated.

Lipolysis is inhibited, lipogenesis is stimulated
Decreased HGO: Decreased gluconeogenesis and glycogenolysis.
Ketogenesis is inhibited.

Question 24

Complications of DM?

Answer 24

1- Macrovascular: This affects the large blood vessels in the body, including stroke, heart attack and MI, and peripheral vascular disease (e.g. limb ischaemia).
2- Microvascular Disease: This affects the small blood vessels in the body:
Diabetic Neuropathy
Diabetic Nephropathy
Diabetic Retinopathy