Exercise and Glycaemic Control

Question 1

What happens when you exercise animals that don’t have insulin signalling?

Answer 1

These animals still get glucose uptake

Question 2

What happens when you combine exercise and insulin to animals that don’t have insulin signalling?

Answer 2

There is a huge synergistic effect. This is far greater than just exercise

Question 3

Why is it advisable to consume carbohydrates immediately after exercise?

Answer 3

Because there are many GLUT4 receptors on the cell membrane. These remain here for ~30 mins.

Question 3

How is AMPK phosphorylated and made active?

Answer 3

By elevating AMP levels (or Ca2+)

Question 3

What protein helps vesicles of GLUT4 transporters to translocate to the membrane?

Answer 3

Rab-GTP

Question 4

What protein converts Rab-GTP to Rab-GDP, in its inactive state?

Answer 4

TBC1D4

Question 5

How does insulin lead to greater Rab-GTP levels?

Answer 5

Insulin binds to insulin receptors on cell surface membrane, signals through a cascade of events, Akt is activated which subsequently phosphorylates TBC1D4, knocking it out - meaning more of the Rab protein ends up as GTP.

Question 6

Does a single-bout of exercise improve the uptake of glucose in skeletal muscles?

Answer 6

Yes, but only transiently (not-permanently)

Question 7

What effect does exercise have on plasma membrane glucose transporters?

Answer 7

Exercise transiently increased concentration of transporters in cell membrane

Question 8

What is AICAR?

Answer 8

A molecule that, when broken down, forms ZMP which has an extremely similar structure to AMP

Question 9

When measuring the effect of AICAR perfusion on GLUT4 translocation, what results are shown?

Answer 9

AICAR increases GLUT4 translocation = more GLUT4 is found on the cell membrane than in the micro-vesicle after exercise

Question 10

Knowing the effects AICAR has on GLUT4 translocation, what does this tell us about AMPK?

Answer 10

AMPK causes GLUT4 translocation.

We know this because AICAR is acting as AMP which stimulates AMPK

Question 11

How does exercise/muscle contraction lead to increases translocation of GLUT4?

Answer 11

When a muscle contracts, CA2+ and AMP levels increase, both of which stimulate AMPK. AMPK stimulates TBC1D4 protein, thus causing increased Rab-GTP, therefore causing an increase in GLUT4 translocation.

Question 12

HOW does a single bout of exercise transiently improve glucose uptake in skeletal muscle?

Answer 12

• Increased perfusion of active muscle increases exposure to target
  tissue
• Translocation of Glut 4 to cell membrane
• Sensitisation of insulin response (Phosphorylation of TBC1D4)
• Increased expression of Glut 4 gene
• Increased glycogen synthase activity

Question 13

What is the difference between fat uptake between a normal healthy muscle and one in an unhealthy/diabetic?

Answer 13

Same amount of fat transporters (CD36), just more on membrane and less in cell for obese people. This mean this muscle’s more likely to take up fat = elevated TAG stores inside muscle

Question 14

How does training improve mitochondrial biogenesis?

Answer 14

Exercise increases Ca2+ and AMP, activating AMPK, which activates transcription factor (TF) to move into nucleus and attach to gene PGC-1a. Switching on this gene produces factors which will increase mitochondrial biogenesis.

Question 15

What effect does exercise have on PGC-1a in humans?

Answer 15

Exercise induces a dramatic transient increase in PGC-1a transcription and mRNA content in human muscles.

Question 16

What does high IMTG in obese individuals lead to?

Answer 16

Accumulation of lipid derivatives and subsequent inhibition of insulin signalling

Question 17

AMPK is a key enzyme in many processes involved in exercise and glycaemic control. State the actions of AMPK.

Answer 17

• Increased synthesis of GLUT4
• Phosphorylates TBC1D4 causing increased GLUT4 translocation
• Increased fat oxidation (blocks malonyl-CoA allowing for more CPT protein)
• Activates PGC-1a allowing for increased mitochondrial biogenesis