Module 3 - Carbohydrate Metabolism Flashcards

1
Q

Carbohydrates:

  • What are they used for?
  • When are they used?
A
  • Used for energy or ATP generation needed by contracting muscles
  • Key substrate during high intensity sprint type exercise, and during more prolonged exercise at a moderate- to high-intensity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Carbohydrate stores

note: endogenous is internal

A
  • Body’s endogenous stores are not large
  • Stored in liver and skeletal muscle as glycogen
  • A glycogen particle in skeletal muscle can contain ~30,000 individual glucose molecules linked together via the core enzyme glycogenin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What happens to glycogen during exercise?

A
  • Glycogen content of active contracting muscle cells is reduced
  • Glycogen is broken down through glycogenolysis which releases the individual glucose molecules from the core glycogenin protein so it can be used by the muscle through glycolysis and aerobic processes to produce ATP needed for muscle contraction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Carbohydrate stored in skeletal muscle as glycogen

  • % of body’s carbohydrate
  • concentration in mmol/kg.DM
A
  • 80% (~400g) of all body’s carbohydrate is found in skeletal muscle as glycogen
  • Glycogen concentrations in skeletal muscle is 50-500mmol/kg.DM - depending on training status, prior exercise, dietary carbohydrate intake
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Carbohydrate stored in the liver

A
  • Higher concentration of glycogen than muscle
  • Liver is smaller in mass (~1.5kg) compared to skeletal muscle (40-50% of body weight in healthy young men)
  • Amount of liver glycogen is 100g or 10-15% of total carbohydrate stores
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Apart from skeletal muscle and liver, the remainder of carbohydrate circulates in the…

A

…blood or plasma as glucose (5g)

  • When required, the glycogen stored in the liver can be broken down and released into circulation to maintain blood glucose levels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the primary factors that affect the source of carbohydrate for use in the major energy systems which are responsible for the production or resynthesis of ATP?

A

1) exercise intensity
2) exercise duration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

During high intensity sprint type exercise (95-100% VO2max above)

A
  • The muscle prefers “muscle glycogen” as its main fuel source
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

During low intensity exercise (25% VO2max)

A
  • Very little glycogen breakdown occurs
  • Overall contribution of both glycogen and glucose only accounts for 10-15% of total fuel source
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

As exercise intensity increases…

A
  • Both glucose and glycogen become increasingly important as energy substrates
  • Contribution to total energy production rises to 70%+ (85% VO2max)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Figure: During exercise at intensity greater than 60% VO2max

A
  • Blood glucose and muscle glycogen are primary fuels oxidised to produce ATP
  • Fast-twitch motor units are recruited as exercise intensity increases, thus increasing the reliance on carbohydrate as the predominant fuel source
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

During prolonged exercise at moderate- to high-intensity

A
  • Carbohydrates contribute to almost 50% of total energy expenditure
  • At the onset of exercise, the main form of carbohydrate utilised is muscle glycogen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

During prolonged exercise, as duration/time increases…

A
  • Muscle glycogen stores rapidly deplete by 40-60% within the first 90-120 mins
  • Because of this, there is a compensatory increase in the reliance on blood glucose as the primary carbohydrate fuel source
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Classic study that manipulated the diet of individuals over 3 days prior to undertaking a single bout of cycling exercise @ 70% VO2max to fatigue (Bergstrom et al. 1967)

Low CHO diet

A
  • Lower than average pre-exercise muscle glycogen levels
  • Able to cycle at workload for 60 mins before they fatigued
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Classic study that manipulated the diet of individuals over 3 days prior to undertaking a single bout of cycling exercise @ 70% VO2max to fatigue (Bergstrom et al. 1967)

Same individuals were fed a normal CHO diet

A
  • Normal pre-exercise muscle glycogen levels
  • 2 fold higher level of muscle glycogen compared to low CHO diet
  • Able to cycle for ~120 mins (60 mins long than low CHO diet) before fatigue occurred
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Classic study that manipulated the diet of individuals over 3 days prior to undertaking a single bout of cycling exercise @ 70% VO2max to fatigue (Bergstrom et al. 1967)

On the final occasion, individuals were fed a high CHO diet

A
  • Pre-exercise muscle glycogen content was 3-4 timed higher than low CHO diet measures
  • Able to cycle for ~180 mins before fatigue
  • Clearly shows the ergogenic effect of high pre-exercise muscle glycogen content on endurance exercise performance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Earlier studies

A
  • Provided theoretical basis for dietary carbohydrate loading prior to exercise or “glycogen super compensation” as a strategy for athletes to enhance endurance exercise performance
  • Highlight that starting exercise with low or inadequate muscle glycogen levels can have a detrimental effect on exercise performance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Endurance based sports (2+ hrs) and CHO demands

A
  • Demands for adequate CHO as fuel often exceed the endogenous muscle glycogen storage capacity or the athlete’s ability to replenish muscle glycogen stores between events or bouts of intense exercise
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Despite the success of “the legend of gatorade” commercial, it was not until the 1980s that researchers…

A
  • Demonstrated that CHO feeding during prolonged exercise could improve exercise capacity during exercise lasting at least 2 hours or more, when muscle glycogen levels were significantly reduced
  • This research explained how the ergogenic effect of ingesting CHO during exercise was achieved
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Muscle glycogen breakdown during exercise primarily depends on…

A

Exercise intensity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

CHO utilisation during low-intensity exercise

A
  • Rate of CHO breakdown is slow
  • Only a small reduction in muscle glycogen after ~120 mins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

CHO utilisation during more intense or heavy exercise

A
  • Rate of CHO breakdown is much greater
  • Muscle glycogen content almost depleted after 60 mins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

During heavy (60 mins) and moderate (120 mins) intensity exercise, fatigue occurs when muscle glycogen is depleted

A
  • Because of the depleted glycogen, the muscle is not able to produce enough ATP rapidly enough the maintain exercise intensity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Under most exercise conditions, the rate of muscle glycogen breakdown is most rapid during the…

A

…early stages of exercise, when concentration or amount of glycogen in the muscle is at its highest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Muscle glycogen is broken down through a metabolic pathway called…

A

…glycogenolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

The primary rate limiting enzyme that regulates this process is called…

A

…glycogen phosphorylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Glycogen phosphorylase is controlled by…

A

…altering the proportion of the enzyme in the less active ‘b’ (i.e. beta) form and the more active ‘a’ (i.e. alpha) form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

The transformation of phosphorylase ‘b’ to more active ‘a’ form occurs in response to…

A

…an increase in the localised levels of calcium that occur as a result of muscle contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Transformation to the more active ‘a’ form via phosphorylation also occurs in response to hormonal stimulation by…

A

…adrenaline

  • Mediated via activation of beta-adrenergic receptors on the plasma membrane, which is followed by an increase in intracellular second messenger cyclic AMP (cAMP)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Glycogen phosphorylase is also controlled by…

A

…allosteric regulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

The activity of glycogen phosphorylase is increased through a rise in…

A

…the allosteric modulators; ADP, AMP, IMP and Pi

  • These products of ATP use, occur in response to muscle contraction, and ensure the rate of muscle glycogenolysis is closely coupled to ATP demand
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Another thing that can influence glycogen phosphorylase is the…

A

…glycogen concentration

  • High levels of muscle glycogen increase the rate of glycogen breakdown in skeletal muscle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Why is muscle glycogen the preferred fuel source during exercise?

A
  • Glycogenolysis is more energetically efficient (produces more ATP)
  • Acts to modulate glucose uptake from the blood
  • Helps to maintain blood glucose within normal levels in the absence of exogenous CHO intake (which is important under fasting conditions)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What regulates the increase in skeletal muscle glucose uptake during exercise

  • 3 primary steps
A

1) Extracellular (outside the muscle)
- Factors that influence glucose supply to the muscle
- Incl. circulating glucose concentration in the blood/plasma, blood flow to contracting skeletal muscle

2) Membrane
- Factors that influence glucose transport across the plasma membrane or sarcolemma of the muscle
- Primarily regulated by the number or activity of glucose transporters (GLUT4)

3) Intracellular (inside the muscle)
- Factors that influence intracellular glucose metabolism or the processes within the muscle related to glucose utilisation or disposal (glycolysis and oxidative metabolism) or muscle glycogen breakdown (glycogenolysis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Glucose supply = …

A

blood flow x blood glucose concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

A physiological response to exercise is a marked increase in…

A

…blood flow

  • The capillary networks supplying skeletal muscle
  • Muscle blood flow can increase up to 20-fold during intense exercise
  • More glucose is delivered to the working muscle to be taken up by the muscle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

When muscle blood flow is well matched to the metabolic demands of the muscle, the other option available to increase glucose supply to the working muscle is by…

A

…changing the blood glucose concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Normal physiological range of blood glucose concentration

A

4-8mM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

When blood glucose concentration is within normal range, the relationship between glucose concentration and muscle glucose uptake during exercise is…

A

…almost linear

  • Indicates that an increase in glucose concentrations during exercise is proportional to an increase in glucose uptake by muscle
  • e.g. ingesting glucose during exercise can increase or maintain blood glucose levels, resulting in an increase or maintenance in glucose supply or availability to the muscle.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

During prolonged exercise, when blood glucose concentration decreases…

A

…muscle glucose supply and availability for glucose to be taken up by the muscle decreases as well

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

How does glucose get into a cell (esp. skeletal muscle cells)?

A
  • A specialised transporter or protein is used that allows glucose entry across the cell membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

The transport or glucose into cells occurs via…

A

…facilitated diffusion mediated by a family of glucose transporters, given the abbreviated GLUT, and a number to identify the particular transporter isoform

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

GLUT4

A
  • The glucose transporter isoform, that is responsible for glucose transport in skeletal muscle
  • Can also be found in adipose tissue and cardiac muscle

When stimulated, it translocates from a storage site inside the cell, to the cell surface (plasma membrane) where it facilitates the diffusion or uptake of glucose from the blood into the cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

When there is an increase in blood glucose levels in response to consuming a meal or feeding glucose…

A

…this stimulates the release of insulin from the pancreas

  • An increase in the hormone insulin is a physiological feedback mechanism that acts to increase the translocation of GLUT4 to the muscle cell or plasma membrane which increases muscle glucose uptake, which lowers blood glucose levels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

During exercise, circulating insulin levels decrease - why?

A

Due to inhibitory effects of catecholamine’s on insulin secretion from the pancreas

46
Q

During exercise and blood glucose transport

A
  • Muscle contraction has ability to take up glucose from the blood
  • Stimulation of GLUT4 transporter translocation to cell membrane from intracellular storage sites (different from those affected by insulin)
  • Muscle contraction that stimulates GLUT4 translocation is different from insulin - ensures glucose demand needed to meet energy demand of contracting muscle is still maintained, despite the fact that circulating insulin levels decline during exercise
47
Q

Why exercise is an important clinical treatment for those that suffer insulin resistance or T2D (where insulin mediated glucose uptake is impaired)

A

Because the ability of muscle contraction to increase muscle glucose uptake independently of insulin

48
Q

Mechanisms where muscle contraction can stimulate GLUT4 to mediate glucose uptake into muscle

A

1) Intracellular calcium (Ca2+)

2) Other calcium sensitive signalling proteins

3) Metabolic intermediates

49
Q

Intracellular calcium (Ca2+) and muscle contraction

A
  • Ca2+ is released from sarcoplasmic reticulum (SR) in response to stimulation from motor nerves
  • Increase in intracellular Ca2+ may activate Ca2+-activated enzymes (incl. calmodulin; CaM and calmodulin activated kinases; CaMK) to activate GLUT4 translocation to the membrane
50
Q

Other calcium sensitive signalling proteins and muscle contraction

A
  • Calcium sensitive signalling proteins may be activated to induce GLUT4 translocation
  • Incl. protein kinase C (PKC) and nitric oxide synthase (NOS)
  • NOS mediates blood flood and may mediate glucose supply to the muscle and glucose uptake
51
Q

Metabolic intermediates and muscle contraction

A
  • AMP activated protein kinase (AMPK) is an intracellular signalling protein that acts as sensor of cellular energy charge
  • Reflected by ratios of AMP/ATP and creatine/phosphocreatine which are altered in the contracting muscle
52
Q

During exercise, once glucose has been transported across membrane into the cytosol…

A

…the major fate of glucose is through the metabolic pathways of glycolysis and subsequent oxidation

53
Q

Before glucose can enter the metabolic pathway of glycolysis it is rapidly phosphorylated by…

A

…adding a phosphate group to glucose (G) by the enzyme Hexokinase, to form glucose-6-phosphate (G6P)

  • Acts to trap the ‘free’ glucose inside the cell
  • Ensures concentration gradient of glucose across the membrane is maintained to allow glucose to enter the cell
54
Q

The concentration of free glucose inside skeletal muscle is low, which suggests that glucose transport…

A

…is limiting to glucose metabolism, since glucose is phosphorylated almost immediately as it enters the cell

55
Q

When blood flow in muscle is high, there are…

A

…adequate GLUT4, then glucose phosphorylation can limit glucose uptake

56
Q

Glucose-6-phosphate (G6P)

A
  • Intermediate metabolite that can influence glucose uptake into the cell
  • Not used in glycolysis
  • Increase of G6P in the muscle cell can feedback to inhibit the enzyme hexokinase
  • Indirectly this acts to limit or reduce glucose transport into the muscle cell
57
Q

Research shows there is an inverse relationship between muscle glycogen availability and glucose uptake

A
  • An increase in muscle glycogen breakdown = increases G6P, which acts to inhibit glucose uptake into muscle
  • With exercise duration, muscle glycogen levels are reduced producing less G6P, which allows for more glucose to be taken up into muscle
58
Q

In skeletal muscle generation of ATP via aerobic oxidation of CHO = a series of metabolic pathways - This first of these metabolic pathways is glycolysis

A
  • Uses glycogen or glucose as its starting substrate, which are converted to the intermediate metabolite, G6P
  • G6P then passes through a series of reactions that form the glycolytic pathway
  • The end product is pyruvate as it has two major fates
59
Q

2 major fates of pyruvate (end product of glycolysis)

A

1) Anaerobic glycolysis -> Lactate

  • During short-term high-intensity exercise when ATP demand is high
  • When rapid ATP production and mitochondrial oxidation is limited = pyruvate is converted to lactate

2) Aerobic glycolysis -> Carbon dioxide + water

  • When O2 availability is not limited (e.g. long slow run)
  • Pyruvate can be transported into mitochondria, and is completely oxidised or broken down to form carbon dioxide and water
60
Q

Oxidative phosphorylation

A
  • Occurs in mitochondria
  • Includes citric acid cycle and electron transport chain
  • Use pyruvate produced from glycolysis, and break it down in the mitochondria to the end products of carbon dioxide and water
  • In doing so, it produces ATP to enable muscle contraction
61
Q

Pathways of oxidative phosphorylation

A

1) Glycolysis

  • In cytosol to generate energy in form of ATP
  • Produces pyruvate for oxidation in mitochondria, along with NADH (a key energy transfer intermediate or electron chain that is needed for ATP production in step 4)

2) Pyruvate processing

  • Before pyruvate can be oxidised, it must be converted to acetyl-CoA
  • Regulated by the enzyme pyruvate dehydrogenase (PDH)

3) Citric acid cycle

  • A key energy-producing pathway in mitochondria that connects CHO and fat metabolism, through the breakdown of acetyl-CoA
  • Generates ATP, carbon dioxide and key electron carriers (NADH, FADH2) for ATP production

4) Electron transport chain

  • Utilises NADH and FADH2 generated by steps 1-3, along with oxygen to produce ATP and water
62
Q

Before pyruvate can be utilised in the mitochondria, it must be converted to…

A

…acetyl-CoA

  • The rate of aerobic ATP production in the mitochondria is influenced by this rate limiting reaction, which is regulated by the enzyme pyruvate dehydrogenase (PDH)
63
Q

Acetyl-CoA is a common intermediate substrate for ATP production for both CHO and fat metabolism. So understanding the control of PDH is important for CHO oxidation, but also because it…

A

…regulates Acetyl CoA levels and the interaction between fat and CHO metabolism during exercise

64
Q

Pyruvate dehydrogenase is controlled by altering the proportion of the enzyme in the…

A

…inactive vs active form

65
Q

In resting muscle, where fat is the major fuel source used to make ATP, pyruvate dehydrogenase is…

A

…predominantly in the inactive (PDHb) form

66
Q

At the onset of exercise, pyruvate dehydrogenase is…

A

…converted from the inactive form to the active form (PDHa)

67
Q

In response to exercise, the activation of PDH…

A
  • Is quick (less than 1 min)
  • Level of PDH activation is graded depending on intensity of exercise
  • Rapid activation of PDH may limit the amount of lactate produced by glycolysis
68
Q

With an increase in duration of exercise, PDH activation…

A

…plateaus early in exercise (10-120 min) and then declines with exercise duration (240 min)

  • Occurs due to a decrease in CHO availability and increased reliance on fat as an energy source for ATP production
69
Q

Given the importance of pyruvate dehydrogenase (PDH) in regulating the rate of aerobic ATP production in the mitochondria it is important to understand its regulation

A
  • Regulation of this enzyme occurs through covalent phosphorylation, where a phosphate group can be added (by a protein kinase) or removed (by a protein phosphatase) from the enzyme
70
Q

Under resting conditions, pyruvate dehydrogenase is in its ___ state?

A
  • Inactive (PHDa) and has the phosphate group attached (phosphorylated by pyruvate dehydrogenase kinase)
71
Q

With the onset of exercise, pyruvate dehydrogenase is converted from the inactive state to the ___ state?

A
  • Active (PDHa) by removing the phosphate group (dephosphorylated by pyruvate dehydrogenase phosphatase)
  • Pyruvate is converted to Acetyl CoA
72
Q

At the onset of exercise, pyruvate dehydrogenase is activated or converted from the inactive PDHb to the active PDHa by localised changes in muscle metabolites that allosterically regulate the enzymes that control the phosphorylation status of PDH. These include:

A

1) An increase in calcium (Ca2+) from muscle contraction

2) An increase in ADP that reflects an increase in ATP demand

3) An increase in the substrate pyruvate as a result of an increase in glycolysis

73
Q

In combination, these localised factors increase the activation of pyruvate dehydrogenase to convert pyruvate to Acetyl CoA which will ultimately…

A

…drive CHO oxidation in the mitochondria and increase aerobic ATP production for muscle contraction

74
Q

As exercise continues the level of pyruvate dehydrogenase activity can be fine-tuned by feedback processes to…

A

…ensure that the overall activation of pyruvate dehydrogenase is matched to the muscle cells demand of requirement for ATP

75
Q

This fine turning occurs by localised changes in muscle metabolites that allosterically regulate the enzymes that control the phosphorylation status of PDH to lower the activity of pyruvate dehydrogenase by conversion of the enzyme into inactive PDHb. These include:

A

1) An increase in Acetyl CoA and NADH, the end products of the pyruvate dehydrogenase reaction

2) An increase in ATP that reflects an adequate ATP supply from the mitochondria for the contracting muscle

76
Q

Maintenance of blood glucose levels

Euglycaemia

A

Normal blood glucose levels in blood

77
Q

Maintenance of blood glucose levels

Hyperglycaemia

A
  • High blood sugar
  • Too much glucose (sugar) in your blood
78
Q

Maintenance of blood glucose levels

Hypoglycaemia

A
  • Low blood glucose
  • Not having enough glucose in the blood
79
Q

Why is the liver glucose production important during exercise?

A
  • For blood glucose levels to be maintained, there needs to be a source of glucose to replace the glucose being taken up by the muscle
  • The liver is the only tissue that is capable of significant glucose production
  • Prevents hypoglycaemia and maintains blood glucose availability
80
Q

The intensity (A) and duration (B) of exercise are the primary factors that affect liver glucose production during exercise

A

A) Increase in intensity = concomitant increase in liver glucose production

  • Light to moderate intensity increases liver glucose production by 2-3 fold compared to rest
  • Strenuous exercise increases liver glucose production by up to 4 fold+

B) During exercise at constant low-to-moderate intensity that may last hours:

  • Initial increase in liver glucose production to a level that can be sustained for at least 2hrs
  • After 3hrs+, liver glucose production gradually declines
81
Q

Liver glucose production during strenuous exercise or early onset of exercise

A
  • Can exceed rate of muscle glucose uptake
  • Results in hyperglycaemia (increase in blood glucose levels)
82
Q

Liver glucose production during more moderate and prolonged exercise

A
  • Unable to match the rate of glucose uptake by contracting muscle
  • Results in hypoglycaemia (decrease in blood glucose levels) - may contribute to fatigue
  • Ingestion of CHO has been shown to be an effective strategy to enhance endurance performance by maintaining blood glucose availability and high rates of muscle CHO oxidation
83
Q

Production of glucose by the liver occurs through two processes:

*Both produce glucose and maintain blood glucose homeostasis over range of exercise intensities and durations

A

1) Glycogenolysis - liver releases glucose into circulation from breakdown of stored liver glycogen

2) Gluconeogenesis - liver takes up non-glucose precursors from circulation in form of lactate, pyruvate, glycerol and some amino acids, and converts these to glucose

84
Q

Regulation of liver glucose production during exercise:

During low intensity exercise…

A
  • Changes in plasma levels of pancreatic hormones, insulin and glucagon
  • Change in insulin-to-glucagon ration are crucial for increase in liver glucose output
  • Plasma insulin levels decrease
  • Plasma glucagaon levels increase
85
Q

Exercise induced changes in insulin and glucagon account for a major proportion of the increase in liver glucose production during exercise primarily by…

A

…acting to promote liver glycogen breakdown (glycogenolysis) and stimulating the release of gluconeogenic precursors for their conversion to glucose in the liver

86
Q

Regulation of liver glucose production during exercise:

During higher exercise intensities

A
  • Increased plasma adrenaline and sympathetic neural activity
  • Increase in circulating adrenaline increases liver glycogenolysis through activation of liver glycogen phosphorylase
87
Q

Changes in ___ ___ also play an important role in regulating liver glucose production, with small decreases in blood glucose acting to increase liver glucose production during the early stages of exercise through classical ___ regulation.

A
  • Blood glucose, feedback
  • Increase in blood glucose availability can also inhibit the exercise-induced rise in liver glucose production
88
Q

The increase in liver glucose production during exercise may also occur in parallel with activation of the contracting skeletal muscles, the cardiorespiratory responses and the neuroendocrine centres that modulate many metabolic processes, such that there is ‘___- ___’ stimulation of the liver, particularly at ___ ___ intensities.

A
  • Feed-forward; higher exercise
89
Q

How ingesting CHO during exercise improves exercise performance

Classic study, subjects cycled to fatigue whilst ingesting every 20 minutes either a placebo or a carbohydrate (CHO) solution.

A

1) The placebo trial
- Plasma glucose levels declined significantly
- Fatigued after ~3hrs

2) The CHO trial
- Glucose levels remained constant, which prevented hypoglycaemia
- Cycled for another hour before fatigue

90
Q

How ingesting CHO during exercise improves exercise performance

In the classic study, what happened when subjects ingested CHO during exercise?

A
  • Increased availability of circulating glucose to contracting muscle
  • Maintenance of high rate of muscle glucose uptake and muscle CHO oxidation
  • Able to sustain exercise intensity and delay the onset of fatigue
91
Q

How ingesting CHO during exercise improves exercise performance

Conclusions drawn from the classic study

A
  • Ingestion of CHO during exercise does not spare of delay the use of muscle glycogen - as glycogen levels were reduced to a similar level in both the placebo and CHO groups
  • Ingestion of CHO was able to maintain glucose availability as primary energy source for the contracting muscle and to delay onset of fatigue
92
Q

Since this study was performed (Coyle et al, 1986), additional studies have been undertaken to further determine “how” ingesting carbohydrate during exercise improves exercise performance.

A
  • Consuming CHO before of during exercise can suppress or reduce liver glucose production
  • This occurs through feedback mechanisms due to direct inhibitory effects of circulating glucose on liver glucose production or changes in glucoregulatory hormonal environment that acts to spare liver glycogen
93
Q

Sparing the use of liver glycogen in combination with ingestion of glucose acts to…

A
  • delay onset of hypoglycaemia
  • ensure blood glucose can contribute to maintain rate of muscle CHO oxidation during exercise, as muscle glycogen stores are depleted with exercise duration
94
Q

Carbohydrate metabolism and performance in response to exercise training

There is large body of research to demonstrate that endurance training ___ the reliance on carbohydrate as a source of energy during prolonged moderate intensity exercise.

A
  • Due to decrease in muscle glycogen utilisation and a reduction in production and utilisation of circulating glucose
  • Improvement of performance can be achieved by minimising the chance of depleting muscle glycogen stores (hypoglycaemia)
95
Q

Muscle glycogen utilisation and exercise training

Pre-exercise concentrations in endurance-trained muscle

A
  • Are higher when compared to sedentary individuals. However, the rate of muscle glycogen use (glycogenolysis) is reduced after training
96
Q

Muscle glycogen utilisation and exercise training

Figure shows a reduction in muscle glucose-6-phosphate during exercise

A
  • Provided evidence to support lower muscle glycogen breakdown following training
97
Q

The effect of exercise training on muscle glycogen use during exercise is likely explained by smaller changes in…

A
  • Local muscle metabolites (AMP, Pi)
  • Circulating adrenaline levels that regulate glycogen phosphorylase
98
Q

Glucose uptake during exercise after training

The rate of muscle glucose uptake during exercise is reduced following either short (10 days) or long term (12 weeks) endurance exercise training. This occurs primarily due to…

A

…a reduction in the number of exercise mediated GLUT4 that translocate to the plasma membrane following training

  • This reduction in GLUT translocation following exercise training occurs despite the fact that endurance exercise training results in an increase in the total content of skeletal muscle GLUT4 transporters.
99
Q

Muscle carbohydrate oxidation during exercise after training

The major mechanism responsible for the training induced changes in exercise metabolism is believed to be the result of an ___ in skeletal muscle oxidative capacity that ___ fat oxidation and subsequently ___ the demand on carbohydrate energy sources

A
  • Increase; enhances; reduces
  • Reduction in CHO oxidation following a period of training, results in a lower RER at the same relative exercise intensity
100
Q

Reduction in carbohydrate oxidation during exercise likely acts to…

A

…reduce glycolytic flux and pyruvate dehydrogenase activation

  • short term endurance training results in the production of less pyruvate and lactate, and a reduction in pyruvate oxidation following exercise at 75%VO2 max when compared to pre-training levels
101
Q

Liver glucose production during exercise after training:

Endurance exercise training ___ total liver glucose production during exercise

A

Reduces

  • This reduction in liver glucose production following training, is mostly due to a reduction in liver glycogen utilisation (glycogenolysis)
  • Effect of exercise training on gluconeogenesis during exercise appears to be minimal
102
Q

The training induced reduction in liver glucose production during exercise is likely ___ to an overall reduction in skeletal muscle carbohydrate oxidation during exercise with exercise training which subsequently reduces the demand for glucose by the contracting muscle

A

Secondary

103
Q

The reduction in liver glucose production following exercise is also likely due to hormonal changes

A
  • Exercise blunts the glucoregulatory hormonal responses to exercise
  • Normal increases in plasma adrenaline and glucagon, and decreases in insulin, that usually stimulate liver glucose production during exercise are lower following exercise training.
104
Q

Heat stress and CHO metabolism:

Heat stress must be large

A
  • Difference in core temp must exceed 0.5C to cause change in metabolism
105
Q

Heat stress and CHO metabolism:

Anaerobic metabolism + training in 20C vs 40C (febbraio et al. 1994)

A
  • Increases
  • Anaerobic metabolites (i.e. ADP, AMP, IMP, NH3, lactate, Creatine) increase to a greater extent
  • Nearly double lactate accumulation in T40 (training in 40C)
106
Q

Heat stress and CHO metabolism:

Aerobic metabolism - steady state exercise in 20C vs 40C (Febbraio et al, 1994)

A
  • No change in O2 consumption
  • Increase in CHO oxidation - shown by increased RER ratio
107
Q

Heat stress and CHO metabolism:

Muscle glycogenolysis: 15 mins bouts of exercise in heat vs cold (fink et al, 1975)

A
  • Muscle glycogen levels reduced in heat group
  • Muscle glycogen use is elevated in heat - increased CHO utilisation
108
Q

In heat stress, there is an increase in CHO oxidation and lactate accumulation, and one major contributor to this is…

A

…an increase in glycogenolysis

  • A greater utilisation of glycogen
109
Q

With heat stress, there is a ___ use of exogenous CHO

A
  • Decreased
  • Increased CHO use in heat is due to increased use of muscle glycogen use, not blood glucose.
110
Q

Fat and CHO oxidation during exercise in the heat (compared to cool)

A
  • Reduced fat oxidation
  • Increased CHO oxidation
  • Increased use of stored glycogen in muscle
111
Q

Heat stress and glucose production

A
  • Increased hepatic glucose production (HGP) -> Increased blood glucose concentration
  • Hyperglycaemia
  • Change in hormonal regulation of the liver (epinephrine, cortisol, glucagon), which are elevated in the heat
112
Q

up to 2nd heat stress video

A