Session 11: Metabolic and Endocrine Control During Special Circumstances

Question 1

Metabolic fuels normally available in blood.

Answer 1

Glucose and fatty acids.

Question 2

In which parts of the body can fatty acids not be used as fuel?

Answer 2

Red blood cells Retina of the eye Brain CNS

Question 3

Metabolic fuels available under special conditions such as starvation.

Answer 3

Amino acids Ketone bodies Lactate

Question 4

What hormones increase fuel concentrations?

Answer 4

Glucagon Adrenaline Growth hormone Cortisol

Question 5

What hormones decrease fuel concentrations?

Answer 5

Insulin.

Question 6

What is glucose stored as?

Answer 6

Glycogen.

Question 7

What are fatty acids stored as?

Answer 7

TAGs

Question 8

Where is glycogen stored? How much is stored?

Answer 8

In liver and muscles. Around 400g in total. Around 300g of it stored in muscles and approx. 100g of it stored in liver.

Question 9

Acute effects of hypoglycaemia.

Answer 9

Trembling Weakness Tiredness Headache Sweating Sickness Tingling around lips Palpitations Changes in mood Slurred speech Stagerring walk

Question 10

Effects of feeding.

Answer 10

Increased glucose uptake Storage of glucose as glycogen in liver and muscle Promotes amino acid uptake and protein synthesis in liver and muscle. Promotes lipogenesis and storage of fatty acids as TAGs in adipose tissue.

Question 11

Effects of fasting.

Answer 11

Glycogenolysis Lipolysis Gluconeogenesis

Question 12

Explain the key features of metabolic control from feeding to starvation.

Answer 12

Glucose and fat available from gut during the first few hours after feeding (2 hours ish) After 2 hours glucose and fats are no longer absorbed and the blood glucose necessary for the brain and red blood cells etc… is mainly drawn from glycogen stores. Other metabolic activity which are not dependent on blood glucose are maintained by fatty acids. At around 8-10 hours the glycogen storage deplete meaning that the brain needs to get its glucose elsewhere. This is now done by gluconeogenesis where the brain gets its glucose from amino acids, glycerol and lactate. Later on during starvation more proteolysis occurs but more importantly the brain starts to be able to utilise ketone bodies as a fuel which reduces the need for glucose.

Question 13

Anabolic hormones.

Answer 13

Insulin and growth hormone where it increases protein synthesis.

Question 14

Catabolic hormones.

Answer 14

Glucagon Adrenaline Cortisol Growth hormone where it increases lipolysis and gluconeogenesis (somewhat catabolic) Thyroid hormones

Question 15

What processes stop the release of insulin.

Answer 15

Gluconeogenesis Glycogenolysis Lipolysis Ketogenesis Proteolysis

Question 16

Label

Answer 16

Question 17

Explain what happens in energy starvation.

What death is related with energy starvation?

Answer 17

Reduction of blood glucose stimulates release of cortisol from adrenal cortex and glucagon from pancreas.

Gluconeogenesis and breakdown of protein and fat occurs.

There is a reduction in the insulin to anti-insulin ratio which is due to cortisol. This prevent most cells from using glucose and fatty acids.

Glycerol from fat provides important substrate for gluconeogenesis reducing the need for breakdown of proteins.

Liver starts to produce ketone bodies. Brain uses glucose right now but will start use ketone bodies as well.

Kidneys begin to contribute to gluconeogenesis.

When the fat stores deplete protein will start to be used.

Death related to loss of muscle mass and resp. muscle infections.

Question 18

Explain the fetal growth throughout pregnancy.

Answer 18

1/3rd of fetal growth occurs over the first 2/3rds of pregnancy.

2/3rds of fetal growth occurs over the last 1/3rd of pregnancy.

Question 19

What are the two main phases of pregnancy?

Answer 19

Anabolic phase and catabolic phase.

Question 20

Explain each phase of pregnancy.

Answer 20

Anabolic phase is early pregnancy where the mother increases their maternal fat stores* and there is a *small increase in level of insulin sensitivity. This is to prepare for rapid growth rate of foetus, birth and for subsequent lactation.

In late pregnancy catabolic phase will occur. There is now a decreased insulin sensitivity* and therefore an *increased insulin resistance.

Increase in insulin resistance results in an increase in maternal glucose and free fatty acid concentration.

Question 21

Briefy explain placental transfer.

Answer 21

Most substances transfer by simple diffusion down concentration gradients.

Glucose is the principal fuel for foetus and transfer facilitaed by transporters which is mainly GLUT 1.

Question 22

What is the fetoplacental unit?

Answer 22

The placenta, fetal adrenal glands and fetal liver of the foetus which forms a new endocrine entity to ensure the foetus own survival.

Question 23

Explain the relationship between the placenta and the maternal hypothalamic pituitary axis.

Answer 23

The placenta secretes a wide range of proteins that can control the maternal hypothalamic pituitary axis and it does so mainly by influencing the release of corticotropin releasing hormone (CRH).

Oestriol and progesterone are two important placental steroid hormones as well.

Question 24

Why does the anabolic phase of pregnancy occur? (Chemically)

Answer 24

Due to an increase in the levels of insulin resulting in an increase of the insulin/anti-insulin ratio which promotes an anabolic state in the mother that results in an increased nutrient storage.

This promotes rapid growth rate of the foetus, birth and subsequent lactation.

Question 25

What happens to the insulin/anti-insulin ratio in late pregnancy and why?

Answer 25

In the growing foetus there is an increase of anti-insulin hormones produced which even though there is a continued production of insulin from the mother it will lower the insulin/anti-insulin ratio.

Question 26

Effects of anti-insulin hormones produced by foetus on the mother.

Answer 26

CRH increases which leads to more increase of ACTH and cortisol.

Also levels of human placental lactogen and progesterone increases.

This can lead to transient hyperglycaemia after meals as there is an increase in insulin resistance.

Question 27

Why might hypoglycaemia occur in late pregnancy and why?

Answer 27

It can occur between meals and at night because of the continuous fetal draw of glucose.

Question 28

What happens to insulin secretion in pregnancy?

Answer 28

Increased appetite -> more glucose ingested.

Oestrogen and progesterone increase the sensitivty of maternal pancreatic beta-cells to blood glucose.

This leads to beta-cell hyperplasia and hypertrophy.

This forms an incrased insulin synthesis and secretion.

Question 29

What are the consequences of the beta-cells not responding accordingly to the pregnancy.

Answer 29

Blood glucose may become seriously elevated and gestational diabetes may develop.

Question 30

Clinical implications of gestational diabetes.

Answer 30

Increased incidence of miscarriage.
Increased incidence of congenital malformation (4x higher)

Fetal macrosomia (big baby)

Disproportionate amount of adipose around shoulders and chest which can lead to shoulder dystocia and further on to Erb’s Palsy.

Associated with hypertensive disorders such as gestational hypertension ad preeclampsia.

Question 31

Explain why gestational diabetes might occur.

Answer 31

The starting point of insulin resistance before the pregancy is crucial as to whether the woman will develop gestational diabetes during pregnancy.

This means that a woman with high insulin resistance and women with pre-diabetes are at a higher risk of developing gestational diabetes.

Also a lot of women with gestational diabetes will later develop type 2 diabetes later in life.

Question 32

3 known underlying causes of gestational diabetes.

Answer 32

Autoantibodies similar to those characteristics of type 1 DM (Rare)

Genetic susceptibility similar to maturity onset diabetes (Very rare)

Beta-cell dysfunction in setting of obesity. and chronic insulin resistance.

Question 33

Risk factors of gestational diabetes.

Answer 33

Maternal age (Over 25 yrs)

BMI over 25 kg/m2

Race and ethnicity (more common in asian, black and hispance ethnic groups)

Personal or family history of diabetes

Family history of macrosomia

Question 34

Management of gestational diabetes.

Answer 34

Dietary modification including calorific reduction in obese patients.

Insulin injection if persistent hyperglycaemia is present.

Regular ultrasound to ensure foetus is well.

Question 35

What does the metabolic response to exercise depend on?

Answer 35

Type of exercise (which muscles are used)

Intensity and duration of exercise

Physical condition and nutritional state of individual

Question 36

Give the rough metabolic rate and total energy expenditure in the following:

Resting metabolic rate

100m sprint

1500m race

Marathon (42 km)

Answer 36

RMR: 4kJ per minute

100m: 200 kJ per minute and 30kJ in total
1500m: 140kJ per minute and 500kJ in total

Marathon: 80kJ per minute and 10000kJ in total

Question 37

What is the main fuel used during exercise?

Answer 37

ATP

Question 38

How long would ATP stores last during a sprint? (In theory)

Answer 38

2 seconds

Question 39

How come we can then sprint for more than 2 seconds?

Answer 39

Because ATP is rapidly resynthesised at a rate that meets the metabolic demand.

The ATP concentration would never fall below 20% because of the regeneration.

Question 40

How does muscle ATP turnover differ compared to resting, marathon and 100m sprint.

Answer 40

0. 06 mmol/sec/kg during resting
1. 2 mmol/sec/kg during marathon
2. 0 mmol/sec/kg during sprint

This means that there is a 50 fold increase from rest to sprint.

Question 41

What is responsible for the use of ATP during exercise?

Answer 41

70% is due to myosin ATPase for the contraction of muscles.

The remaining 30% comes from cellular processes such as maintaining ionic graidents across the cell membrane.

Question 42

Where does the energy come from to produce ATP?

Answer 42

Creatine phosphate

Glycolysis

Oxidative phosphorylation

Muscle glycogen

Blood glucose

Fatty acids

Question 43

Explain how and when creatine phosphate stores provide energy.

Answer 43

Creatine phosphate rapidly replenish ATP to provide immediate energy during 100m sprint. This is the initial burst of energy.

Creatine phosphate -> creatine by the use of ADP to ATP with the help of creatine kinase.

The reverse reaction is also possible but it uses ATP so it is not used here.

Question 44

How is ATP replenished after creatine phosphate stores are used?

Answer 44

By glycolysis and oxidative phosphorylation.

To use glycolysis and oxidative phosphorylation energy stores are needed to be used. Such as blood glucose, glycogen from muscle and fatty acids.

Question 45

Explain the use of muscle glycogen during exercise.

Answer 45

After creatine phosphate stores are used muscle glycogen can be used as fuel to replenish ATP.

Intensive exercise which is anaerobic can be sustained by muscle glycogen for up to 2 minutes.

If the exericse is low intensity O2 can be supplied for complete oxidation of glucose and glycogen stores from the muscles and liver. Then it can last for over 60 minutes.

Question 46

Briefly walk through glycogen to glycolysis and onwards.

Answer 46

Muscle glycogen undergoes glycogenolysis where glycogen phosphorylase produced glucose-6-P.

Glucose-6-P is then used in glycolysis where phosphofructokinase is the main regulator stimulated by high AMP and inhibited by high ATP.

Pyruvate then can enter TCA cycle in aerobic (low intensive) exericse

Lactate forms in the case of anaerobic exercise

Question 47

Explain the role of blood glucose in exercise.

Answer 47

During aerobic exercise the liver is a key player.

Exercise result in an increased blood glucose production through glycogenolysis and gluconeogenesis.

The liver recycles lactate produced by anaerobic metabolism with the use of Cori cycle.

Muscle takes up blood glucose via GLUT4 transporter where insulin promotes translocation to plasma membrane and GLUT1.

Question 48

Explain Cori cycle.

Answer 48

Glucose in liver goes to glucose in muscle.

Glucose in muscle is then converted into lactate.

Lactate goes via blood to the liver.

The lactate which is now in the liver is then converted back into glucose.

Question 49

Explain how insulin independent glucose uptake in exercising muscles.

Answer 49

An increase in AMP stimulates AMPK which results in a signalling cascade that increase GLUT4 translocation to plasma membrane so more glucose can be taken up.

Question 50

When will fatty acids be used as fuel during exercise?

Answer 50

Only used in aerobic conditions.

Question 51

Explain the use of fatty acids in aerobic exercise.

Answer 51

This can theoretically provide enough energy for 48 hours during low intensity exercise.

There is a slow release from adipose tissue. A low rate of ATP production but high capacity for sustained production.

The capacity for uptake across the mitochondrial membrane is limited due to the carnitine shuttle.

Question 52

Explain metabolic response in a 100m sprint.

Answer 52

Short high intensity exercise where oxygen isn’t delivered sufficiently in time to muscles.

Creatine phosphate stores are used first.

Then glycogen stores in muscles are used along with Cori cycle to produce lactate and further use it again and again.

However since O2 can’t be used there is no oxidative phosphorylation occuring. Pyruvate is then turned into lactate via lactate dehydrogenase. There is a build up of lactate and build up of H+ resulting in fatigue.

Question 53

Explain metabolic response in a 1500m middle distance run.

(Explain three phases)

Answer 53

Oxygen is somewhat used to make sustain the metabolic response. This means that aerobic metabolism takes place and due to this fatty acids can be used.

There is however still around 40% anaerobic metabolism.

There are three phases:

Initial start uses creatine phosphate and anaerobic glycogen metabolism.

Long middle phase where ATP is produced aerobically from muscle glycogen.

The final finishing spring relies again on the anaerobic metabolism of glycogen and produces lactate.

So: (Creatine phosphate + glycogen) -> (Aerobic via fatty acids or glucose)

-> (Anaerobic via glycogen again producing lactate)

Question 54

Explain metabolic response in a marathon.

Answer 54

Since it is low intensity and over a long duration most of the exercise is aerobic (95%).

This means that muscle glycogen, liver glycogen and fatty acids will all be used.

Muscle glycogen will deplete in the first minutes. Glucose from liver glycogen will peak at around an hour and then declines steadily. Utilisation of fatty acids rises steadily from 20-30 minutes.

Question 55

Explain the hormonal control of metabolic response over the course of running a marathon of the following:

Insulin

Glucagon

Adrenaline + growth hormone

Cortisol

Answer 55

Insulin levels fall slowly because a rise of adrenaline inhibits insulin secretion.

Glucagon levels will rise leading to glycogenolysis, gluconeogenesis and lypolysis.

Adrenaline and growth hormone levels rise rapidly.
Adrenaline -> glycogenolysis and lipolysis
Growth hormone -> gluconeogenesis and lipolysis

Cortisol rises slowly -> lipolysis and gluconeogenesis.

Question 56

Benefits of exercise.

Answer 56

Body composition changes. Adipose goes down and muscle goes up.

Glucose tolerance improves

Insulin sensitivity of tissues increases (meaning lower insulin resistance)

Blood triglycerides decrease like VLDL, LDL and HDL goes up.

BP falls

Psychological effects feeling of well-being.

Question 57

Label

Answer 57