Integration of Metabolism

Question 1

What % of our body mass is made up of skeletal muscle

Answer 1

40-50%

Question 2

What % of our resting oxygen consumption is from skeletal muscle

Answer 2

20-30%

Question 3

What % of our insulin-mediated glucose disposal comes from skeletal muscle

Answer 3

75%

Question 4

Prolonged increases in blood glucose can lead to what, causing diabetes

Answer 4

Insulin resistance

Question 5

Insulin resistance will lead to de novo lipogenesis. What does this cause

Answer 5

Increased fat levels

Question 6

Describe the Randle’s cycle

Answer 6

an alternating interaction between glucose and FFA metabolism. It explains the inhibition of glucose oxidation by fatty acids

Question 7

Why is glucose oxidation inhibited by FAs- Randle’s cycle

Answer 7

A greater amount of fat through the fat oxidation pathway increases acetyl CoA,
which inhibits PDC.
An increase in citrate also inhibits PFK,
which inhibits glycolysis as a whole.

Question 8

What suggests regulation of FA at PFK

Answer 8

Increased plasma FFA via lipid and heparin infusion

Question 9

What suggests regulation of FA at glut-4

Answer 9

A decrease in glucose uptake during moderate intensity

Question 10

Decreased free ADP and AMP levels suggest regulation at what enzyme in glycolysis

Answer 10

Glycogen phosphorylase

Question 11

Why can the Randle’s cycle be reversed in the fed state?

Answer 11

Both medium and long chain FFAs can’t enter the fat oxidation cycle without the help of carnitine

Question 12

Increasing glucose availability inhibits fat oxidation at which transporter

Answer 12

CPT1

Question 13

To preserve glucose supply to tissues relying on glucose, what stimulates adipose tissue lipolysis + hepatic glucose production?

Answer 13

High insulin/glucose ratio

Question 14

How can CHO intake affect absorption insulin/glucagon ratio

Answer 14

Lower intake = lower ratio

Question 15

What does malonyl-coA do

Answer 15

Inhibits CPT1 and increases glucose flux as a result

Question 16

How are malonyl-coA and the Randle hypothesis linked

Answer 16

As long duration exercise causes no change/increase in Malonyl CoA.. this shows the Randle hypothesis may not be true as this doesn’t fit with it

Question 17

What is insulin secreted from the pancreas in response too? (Other than glucose)

Answer 17

Protein + CHO

Question 18

Give the key steps in insulin signalling/Insulin stimulated glucose uptake

Answer 18

1. glucose arrives at the cell
2. insulin released
3. insulin binds to IRS-1
4. Signal transduction cascade
5. glut 4 translocation
6. glucose enters via facilitated diffusion and undergos glycolysis

Question 19

Describe Carnitine

Answer 19

Carnitine mediates the transport of medium/long chain fatty acids across the mitochondrial membranes, facilitating oxidation. It is a cofactor for CPT1, to allow FFA to enter the mitochondrion, by forming acyl-carnitine.

Question 20

what does carnitine act as a buffer for

Answer 20

a buffer for excess access acetyl-coA groups allowing glycolysis to continue

Question 21

Where in the body is 95% of carnitine found

Answer 21

Skeletal muscle

Question 22

How does carnitine feeding alter CHO/fat metabolism and exercise performance

Answer 22

Feeding carnitine doesn’t enter the muscle very quickly- no effect on performance/metabolism

Question 23

Which fuel oxidation does carnitine increase

Answer 23

Fat oxidation- glycogen sparing

Question 24

Define insulin resistance

Answer 24

The reduced responsiveness of skeletal muscle glucose uptake to normal circulating levels of insulin

Question 25

Other than the responsiveness of skeletal muscle to glucose uptake, where can insulin resistance be present?

Answer 25

• Impaired ability of insulin to stimulate glucose oxidation (via PDC)
• Impaired ability of insulin to stimulate microvascular perfusion
• Impaired ability of insulin to stimulate amino acid uptake into muscle cells
• Impaired ability of insulin to inhibit muscle protein breakdown

Question 26

If IRS-1 is inhibited, what process is inhibited

Answer 26

Glut-4 translocation

Question 27

Give one method of measuring insulin resistance

Answer 27

hyperinsulinemic-euglycemic clamp technique

Question 28

What is the hyperinsulinemic-euglycemic clamp technique

Answer 28

maintaining a high insulin level by perfusion, or infusion with insulin at a set rate. It is a way to quantify how sensitive the tissue to insulin

Question 29

True or False: Insulin sensitivity declines naturally over a lifetime.

Answer 29

True

Question 30

Give 3 general causes of Insulin resistance

Answer 30

an increased energy intake, physical inactivity, and obesity

Question 31

What disease does insulin resistance lead too?

Answer 31

Type 2 diabetes

Question 32

What is metabolic inflexibility?

Answer 32

Switching between substrates. Where we are less good at regulating fat and stay hyperglycaemic.

Question 33

What is the lipid overspill theory?

Answer 33

An individual’s capacity to store lipids in adipose tissue has a set maximal limit. When this is exceeded, excess lipids spill into plasma, elevating plasma FFA and triglyceride levels.

Question 34

Other than glut-4, what else can directly effect fat oxidation via CPT1

Answer 34

AMPK

Question 35

Give 2 methods to treat insulin resistance

Answer 35

1. Weight loss via calorie restriction
2. Endurance exercise training
3. Resistance training
4. Pharmacological to
   a. Increase insulin sensitivity
   b. Or mimic insulin