Integration of Metabolism

Question 1

What is the normal range of blood glucose levels?

Answer 1

100 mg/100 mL - 70 mg/100 mL

Question 2

How is the insulin to glucagon ratio in the fed state?

Answer 2

It’s quite high because insulin is the predominant hormone here.

Question 3

How do insulin levels relate to plasma glucose levels?

Answer 3

It mirrors them so when insulin is high plasma glucose is high. Insulin is secreted when glucose levels are high in order to bring this molecule into the cell.

Question 4

What’s the effect of secreted insulin in the liver?

Answer 4

1. Increased phosphorylation of glucose in the liver
2. Increased glycogen synthesis
3. Increased activity of pentose phosphate pathway
4. Increased glycolysis
5. Increased fatty acid synthesis
6. Increased TAG synthesis

Question 5

What happens to adipose in the fed state?

Answer 5

1. Increase in glucose into adipose tissue
2. Increased glycolysis
3. Increased in pentose phosphate pathway (HMP); more NADPH for reducing power for fatty acids
4. Increase in fatty acid synthesis
5. Increased in chylomicron transport as more food in body
6. Increased in TAG synthesis (VLDL broken down by lipoprotein lipase

Question 6

What happens in skeletal resting muscle in the fed state?

Answer 6

1. Increase glucose uptake from GLUT4
2. Increased glycogenesis
3. More amino acids taken into muscle to make proteins to power contraction NOT a fuel store

Question 7

What happens to the brain in the fed state?

Answer 7

1. Increase in glucose uptake to be used as a form of energy

Question 8

Does the brain have any fuel reserves?

Answer 8

No it doesn’t have any TAGs or glycogen stores, thus it needs to be provided with glucose at all times.

Question 9

What GLUT transporter works in the brain?

Answer 9

GLUT3, which is insulin independent, thus more active when blood glucose levels are relatively high.

Question 10

What happens to the liver in the fasted state?

Answer 10

1. Increased rate of glycogen degradation
2. Increased rate of gluconeogenesis (using the glycogen)
3. Glucose can be transported to other tissue
4. Increased rate of fatty acid oxidation (mobilize fats into liver)
5. Increased in acetyl CoA use to make ketone bodies (used by other tissues when running out of fuel)
6. Increased synthesis of ketone bodies
7. Lactate from skeletal muscle gets moved back into liver to be converted back into pyruvate

Question 11

What happens to adipose in fasted state?

Answer 11

1. Increase in TAG breakdown to mobilize fuel stores (HS lipase and ATGL)
2. Glycerol used for gluconeogenesis liver and brought to other tissues
3. Fatty acids used by other tissues; liver use directly as an energy source or indirectly by packaging them up (glucagon stimulates beta oxidation)

Question 12

What happens to rested skeletal muscle in the fasted state?

Answer 12

1. Switch over to use of fatty acids as energy source
2. Ketone bodies used as well

Question 13

When does muscle use glycogen?

Answer 13

During exercise

Question 14

What happens to the brain during the fasted state?

Answer 14

1. Gluconeogenesis from the liver keeps enough glucose present for the brain to function
2. Switch over to ketone bodies during prolonged fasting

Question 15

What is the effect on the insulin:glucagon ratio in diabetes?

Answer 15

It’s low similar to the fasted state.

Question 16

What are complications of untreated type 1 diabetes?

Answer 16

Hyperglycemia, ketoacidosis, and hypertriacylglycerolemia.

Question 17

Hyperglycemia

Answer 17

High amounts of sugar (glucose) in the blood

Question 18

Ketoacidosis

Answer 18

Not enough insulin being produced, thus the liver breaks down fats for energy and releases ketone bodies. There is a buildup of these in the bloodstream.

Question 19

Hypertriacylglycerolemia

Answer 19

High amounts of fats in the blood.

Question 20

What is the main indication of diabetes?

Answer 20

Elevated plasma glucose concentration.

Question 21

What happens to glucose uptake in diabetes?

Answer 21

Less glucose uptake since low insulin levels. There is no increased membrane expression of translocated GLUT4 transporters.

Question 22

How does hyperglycemia come to be?

Answer 22

There is a reduced uptake of glucose in adipose/skeletal muscle and excess production of it via the liver. This is due to increased glycogenolysis and gluconeogenesis.

Question 23

What happens to fatty acid synthesis in diabetes?

Answer 23

It is inhibited since there is less insulin being produced to activated carboxylase.

Question 24

What happens to fatty acid oxidation in diabetes?

Answer 24

It is activated since the carboxylase is inactive. There is less malonyl CoA being made, thus FA oxidation proceeds and more acetyl CoA is being produced.

Question 25

What does acetyl CoA stimulate?

Answer 25

Gluconeogenesis

Question 26

What happens to adipose metabolism during diabetes?

Answer 26

Fat reserves are being mobilized since glucagon stimulates HS lipase and ATGL. Low levels of insulin prefer this pathway.

Question 27

What happens to the uptake of TAG from the blood in diabetes?

Answer 27

This is lowered since less insulin means lipoprotein lipase isn’t being activated. This enzyme breaks down TAGs into its components so they can be used for energy. Thus there are elevated amounts in the blood.

Question 28

What happens to the large amounts of fatty acids entering the liver from adipose?

Answer 28

The liver can repackage the FAs into TAGs and produce more carrier molecules (VLDL). More fats are placed back into the bloodstream

Question 29

What happens if there is too much acetyl CoA made from FAO?

Answer 29

It makes ketone bodies.

Question 30

How does ketoacidosis result from diabetes?

Answer 30

There is an increased mobilization of FAs from adipose and accelerated FA oxidation in the liver. More acetyl CoA made and the excess makes ketone bodies.

Question 31

How does hypertriacylglycerolemia result from diabetes?

Answer 31

There is an elevated production of VLDL in the liver and there is a low activity of lipoprotein lipase at adipose and skeletal muscle, allowing for TAGs to buildup in the bloodstream.