Integration of Metabolism Flashcards
What % of our body mass is made up of skeletal muscle
40-50%
What % of our resting oxygen consumption is from skeletal muscle
20-30%
What % of our insulin-mediated glucose disposal comes from skeletal muscle
75%
Prolonged increases in blood glucose can lead to what, causing diabetes
Insulin resistance
Insulin resistance will lead to de novo lipogenesis. What does this cause
Increased fat levels
Describe the Randle’s cycle
an alternating interaction between glucose and FFA metabolism. It explains the inhibition of glucose oxidation by fatty acids
Why is glucose oxidation inhibited by FAs- Randle’s cycle
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.
What suggests regulation of FA at PFK
Increased plasma FFA via lipid and heparin infusion
What suggests regulation of FA at glut-4
A decrease in glucose uptake during moderate intensity
Decreased free ADP and AMP levels suggest regulation at what enzyme in glycolysis
Glycogen phosphorylase
Why can the Randle’s cycle be reversed in the fed state?
Both medium and long chain FFAs can’t enter the fat oxidation cycle without the help of carnitine
Increasing glucose availability inhibits fat oxidation at which transporter
CPT1
To preserve glucose supply to tissues relying on glucose, what stimulates adipose tissue lipolysis + hepatic glucose production?
High insulin/glucose ratio
How can CHO intake affect absorption insulin/glucagon ratio
Lower intake = lower ratio
What does malonyl-coA do
Inhibits CPT1 and increases glucose flux as a result
How are malonyl-coA and the Randle hypothesis linked
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
What is insulin secreted from the pancreas in response too? (Other than glucose)
Protein + CHO
Give the key steps in insulin signalling/Insulin stimulated glucose uptake
- glucose arrives at the cell
- insulin released
- insulin binds to IRS-1
- Signal transduction cascade
- glut 4 translocation
- glucose enters via facilitated diffusion and undergos glycolysis
Describe Carnitine
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.
what does carnitine act as a buffer for
a buffer for excess access acetyl-coA groups allowing glycolysis to continue
Where in the body is 95% of carnitine found
Skeletal muscle
How does carnitine feeding alter CHO/fat metabolism and exercise performance
Feeding carnitine doesn’t enter the muscle very quickly- no effect on performance/metabolism
Which fuel oxidation does carnitine increase
Fat oxidation- glycogen sparing
Define insulin resistance
The reduced responsiveness of skeletal muscle glucose uptake to normal circulating levels of insulin
Other than the responsiveness of skeletal muscle to glucose uptake, where can insulin resistance be present?
- 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
If IRS-1 is inhibited, what process is inhibited
Glut-4 translocation
Give one method of measuring insulin resistance
hyperinsulinemic-euglycemic clamp technique
What is the hyperinsulinemic-euglycemic clamp technique
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
True or False: Insulin sensitivity declines naturally over a lifetime.
True
Give 3 general causes of Insulin resistance
an increased energy intake, physical inactivity, and obesity
What disease does insulin resistance lead too?
Type 2 diabetes
What is metabolic inflexibility?
Switching between substrates. Where we are less good at regulating fat and stay hyperglycaemic.
What is the lipid overspill theory?
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.
Other than glut-4, what else can directly effect fat oxidation via CPT1
AMPK
Give 2 methods to treat insulin resistance
- Weight loss via calorie restriction
- Endurance exercise training
- Resistance training
- Pharmacological to
a. Increase insulin sensitivity
b. Or mimic insulin
