Sports nutrition and metabolism Flashcards
Key principle of food first?
Nutrient dense foods can supply balanced mix of micro- and macro-nutrients
Work synergistically to support absorption
Bioactive compounds present in foods - fibre, polyphenols, vitamins
Rationale for ergogenic aids or supplements?
To correct a deficiency Convenience Performance enhancing
Gene doping?
CRISPR technology can edit genes
Not a risk right now, takes a lot of genes to make musculature change
Issues to consider when prescribing a supplement?
Legality - WADA
Safety - toxicity, more not always better, special populations
Contamination of supplements
Consider what their performance/health goals are
How to monitor it through biomarkers
Performance factors to consider?
Type of sport - endurance, team, strengthpower, weight classification/aesthetic
Factors limiting performance
Athlete characteristics
Periodised phase of programme
Environmental conditions
Australian institute of sport - ABCD model?
Supported for use in specific situations using evidence based protocol - A
Deserving of further research and could be considered for provision to athletes under a research protocol or case-managed monitoring situation - B
Have little meaningful proof of beneficial effects - C
Banned or at high risk of contamination with substances that could lead to a positive drug test - D
Class A performance supplements?
Macronutrients Carbohydrate
Protein
Electrolytes
Glycerol Creatine Nitrate
Buffers
β-alanine (β-alanyl-L-histidine) Sodium bicarbonate
Stimulants Caffeine
What is cannabidiol?
One of the many cannabinoids in marijuana or hemp = CBD
Its not THC
Claims (effects) - anti-inflammatory, neuroprotective, analgesic, anxiolytic
Claims (application) - concussion/ sub-concussive injury, performance enhancing (less pain, pacing), sleep enhancing, recovery enhancing
Risk of doping infringement, CBD can be contaminated by THC or other banned cannabinoids
CBD use in rugby?
26% of players using, more older players were using it
Goals were to improve recovery/pain or sleep
Only 14% saw an improvement
Unpublished data also shown that 20mg on CBD had no effect on acute or chronic muscle soreness in rugby players
Conclusions on CBD?
Significant risk of doping charge
Limited evidence of efficacy
Plausible mechanisms of action
More research is needed
How is vitamin D made?
In our skin by converting UVB light, 30 mins per day is enough
Can also be found in lots of food
Cellular effects of vitamin D?
Classical actions -
Calcium homeostasis
Bone metabolism
Neuromuscular function
Non-classical actions - Immune function Cardiovascular function Mitochondrial function Cellular proliferation and differentitation
Is vitamin D deficiency common in athletes?
yes, studies shown especially in indoor athletes
This is also affected by seasonal changes
Roles of vitamin D?
Bone health:
Increases calcium and phosphate absorption
Bone mineral density increases with vitamin D
Muscle function:
Calcium kinetics
myoblast differentiation - muscle regeneration
Muscle weakness evident with vitamins D deficiency
Immune function:
Improved macrophage and monocyte function
Increased upper respiratory tract infection (URTI) rate with a poor fit D status
What is measured as a biomarker to indicate levels of vitamin D within the blood?
25(OH)D
Vitamin D conclusions?
Deficiency or inadequacy is prevalent amongst athletes
Poor vitamin D status is associated with impaired bone health, exercise performance and immune function
Not sure if casual
Vit D3 supplementation may be helpful for those who are deficient, reaching a target serum of 75nmol.L^-1 which is done by having 4000 IU per day
Blood glucose mass (kg), Energy (kJ) and exercise time (min)?
0.01 kg
160 kJ
2 min
Liver glycogen mass (kg), Energy (kJ) and exercise time (min)?
0.08 kg
1280 kJ
16 min
Muscle glycogen?
0.40 kg
6400 kJ
80 min
Fat mass (kg), Energy (kJ) and exercise time (min)?
10.5 kg
388500 kj
4856 min
Protein mass (kg), Energy (kJ) and exercise time (min)?
12 kg
204000 kj
2550 min
Carbohydrate digestion?
In mouth broken down by salivary amylase
Down the oesophagus into the stomach
High levels of acid stop amylase action - no carb breakdown
Move to small intestine where there is pancreatic amylase which breaks carbs down into disaccharides
Sucrase, Lactase and Maltase then break the carbs down into monosaccharides
Monosaccharides transported into the blood and the liver
Monosaccharide absorption for glucose and galactose?
Co transported with Na+ from the intestinal lumen via SGLT 1, through the intestinal wall and into the blood via GLUT 2
Monosaccharide absorption for fructose?
Intestinal lumen through the intestinal wall via GLUT 5, then into the blood via GLUT 2
What does adipose tissue store?
Triglycerides
What does liver store?
80-100g of glycogen but can break this down into glucose and transport in to the blood
This is down by glucose - 6 -phosphatase
What does the blood store in terms of carbohydrates?
4-5mmol/l (20g)
Can be transported into muscle
Muscle carbohydrate storage?
Muscle has 300-400g of glycogen, in athletes can go up to 900 g
Make notes on glycolysis, TCA and ETC for exam most likely?
ok
Is muscle glycogen essential for endurance capacity and obtained from a high carb diet, and features of this?
yes
It also depletes quicker with more intense exercise
Same with liver glycogen
Therefore muscle glycogen is essential for short duration exercise, gets used up so not utilised in longer bouts of exercise
Classical super compensation protocol?
Week before a race you would do one hard bout of training, followed by no training at all and 3 days of low CHO intake, then 3 days of high CHO intake before race day
Problems:
Hypoglycaemia in low CHO = low blood blood sugar
Difficult to find food with no carbs
GI distress
Poor recovery
Poor mental state from no training
Moderate super compensation protocol?
Slowly decrease training, whilst slowly increasing CHO intake
No difference compared to the classical after 60 minutes of exercise
Carb loading prior to squash?
Diet high in CHO resulted in
Increased CHO oxidation
Maintains higher blood glucose
Improves physical performance
Is carb loading worth it?
Yes for:
Repeated sprints
Intermittent sports lasting greater than an hour
Exercise lasting more than 90 minutes
No for:
Short and explosive
Kess apparent if ingesting CHO during exercise
Practical guidelines for carb loading?
Start exercise with sufficient muscle glycogen, don’t need way more
Eating CHO rich for 2 days prior to a race decrease training
EE reduced so not just ear more
A carbohydrate intake of 5-7 g/kg per day seems to be sufficient in the majority of cases (with low EE)
GI athletes need to be careful
CHO intake hours pre exercise?
Maximise glycogen in liver and muscle
Improves performance
CHO are most important 1-4g/kgBM - lower if very close to the event
Avoid low GI and avoid fat, need to get all food out of stomach before running to avoid runners trots
Practice the routine
Physiological effects of CHO intake hours pre exercise?
Transient fall in plamsa glucose at exercise onset
Increased CHO oxidation and accelerated glycogen breakdown
Blunting of Fatty acid mobilisation and fat oxidation - good for short exercise as want to prioritise carbs
Important if cannot take CHO in during exercise
Physiological effects of CHO intake 30-60 min pre exercise?
Causes large rise in plasma glucose and insulin
Which may then lead to hypoglycaemia during exercise
This is due to large rise in plasma glucose and insulin, which can then lead to reactive/rebound hypoglycaemia during exercise
Can manipulate of ingested CHO to help tis (lower are better), also low GI food and just don’t eat
This is hypothetical and performance should be fine
Goals and considerations when taking in CHO during exercise?
Prevention of the depletion of blood glucose, and muscle and liver glycogen
Maintain hydration
Duration of event?
How much CHO? (duration, intensity, GI ability)
Type and form of CHO? (gel /solid/ monosachharide
When you have low carbs do you have to rely on free fatty acids and glycerol more?
yes
Is it possible to have performance benefits from in exercise CHO intake but not see an increase in CHO levels in plasma?
Yes will find out why in a few videos time
Exogenous galactose versus oxidation during exercise?
Higher levels of oxidation of glucose than oxidation
Oxidation of ingested carbohydrate?
It doesn’t keep on getting bigger the more carbs you eat, maxes out round 1g/min can’t digest it quick enough, or absorb it
Rapidly oxidised: (up to 1g/min) - Glucose Sucrose Maltose Maltodextrins Amylopectin
Oxidised at lower rates (up to 0.5g/min)
Fructose (liver) Galactose (liver) AMyose Isomalutose Trehalose
What can be done to increase ingested carb oxidation rate?
Combined ingestion - means that different transporters are utilised
This means there is now very rapidly oxidised carbohydrate mixes ( >1g/min) which are?
Glucose and fructose (>60g/h glucose)
Maltodextrin and fructose (>60g/h maltodextrin)
Glucose, sucrose and fructose (>60g/h glucose and sucrose)
If you can tolerate higher levels of carbs (120g/h) then during hard exercise can reduce exercise induced muscle damage markers such as creatine kinase, lactate dehydrogenase, GOT
Also performance is enhanced by using combinations
Does the infusion of CHO increase exercise performance?
no
Features of brain imaging when glucose compared to a sweetener is used as a mouth rinse, and does glucose increase cycling time?
Glucose activates parts of the brain which improves performance
LAB REPORT IMPORTANT
Glucose increases power and TT time when cycling, works better when you are in a fasted state
Practical application of CHO during exercise?
Mix and match of: Water CHO drinks Gels Bars FOod
Low in fat and fibre
Protein if over 4 hours long
Absolute amount not per bodyweight - it’s about how quickly you can get it in
200ml every 20 min = better than 50ml every 5 min, makes a balance between stomach too full and just right
Practice is most important
Conclusions on CHO use on exercise performance?
CHO can improve endurance capacity over 2 hours, but also high intensity exercise lasting around 75 min
CHO ingested during exercise will spare liver glycogen and can completely block hepatic glucose output
Exogenous CHO oxidation rates of a single CHO peaks at 1-1.1 g.min^-1
Ingestion of multiple transportable CHO can increase exogenous carbohydrate oxidation rates by 20-50%
Features of triglycerides?
Major storage from of fats in the body
3 fatty acids react with one glycerol molecule to produce a triglyceride molecule
This is done via a condensation reaction = esterification (water is removed)
Features of carbon chain length?
Fatty acids vary in (carbon chain) length and can be classified as short (4 or less) (SCFA), medium (6-12) (MCFA) or long (>14) (LCFA)
The longer the chain length, the more solid and less liquid a fatty acid becomes at room temperature
More we eat is long chain fatty acids
Saturated vs unsaturated fatty acids?
saturated = all hydrogen bonds
Unsaturated = missing hydrogen bonds (has double carb bonds)
What are trans fats?
In nature they are cis
Trans form due to processing e.g. heat and light
Essential/non-essential fatty acids?
Essential = can’t be made in the body so has to be obtained by the diet
Non-essential = can synthesis in the body from specific precursors
Omega end = the end away from the Carboxyl complex
Omega number = number of carbons away from the omega end in which the closest double bond occurs
n-3 and n-6 polyunsaturated fatty acids are incorporated into cell membranes, what effect does this have on cell function?
The ratio of n-3/n-6 PUFA in cell membranes leads to different set of intracellular mediators produced
Higher n-3 leads to less inflammatory mediators produced
Studies in illness, disease in human and animal confirm this effect, which is modulated by dietary intake
Features of adipose tissue?
Provides a basically infinite store of energy during exercise
Features of lipoproteins?
Fat has to be transported in aqueous solution (blood)
Done via chylomicrons
You have very low, low and high density lipoproteins
Should learn all of first year cards
ok
Can you generate ATP from fat anaerobically?
NO
Fat must go through complex set of regulatory reactions to get into the mitochondria, then can enter the TCA cycle to produce ATP
So its slower than producing energy from carbs
Describe long chain fatty acids getting into the mitochondria and therefore being able to produce ATP?
Fatty acid translocase/CD36 and fatty acid binding protein take the long chain fatty acids from circulation into the cytosol
Join a pool from the intramuscular triglyceride store as well
The long chain fatty acids are very inert so become activated by Co enzyme A (CoASH), forming Acyl-CoA
This can now enter the mitochondria through the carnitine shuttle, achieved through the CPT1, CACT, and CPT2 enzymes
Ready to undergo beta oxidation to make ATP
This is why fat can’t sustain contractions at 75% VO2 max, it is too sluggish
The athletes paradox?
As we exercise we reduce the amount of adipose tissue we have
Oxidative capacity and insulin sensitivity are markers of good metabolic health
as we exercised more, restricted calories, are metabolic health increases, and if we are inactive, obese and on high fat diets it would decrease
The more fat we get the more is stored as intra myocellular lipids as expected at one end of the scale
As you get leaner the intra myocellular lipids levels drops, but when you keep on training on the scale of athlete they increase above what someone who is obese or type 2 diabetic
In athletes how is the intra myocellular lipids stored in the muscle compared to that of an obese person?
In athletes stored directly proximal to the mitochondria
Also in athlete normally in smaller droplets = larger SA to volume ratio so can be used quicker
Therefore most readily available fat store in the body
Obese individual harder to access the fat and use it effectively
Different types of fat as fuel?
Plasma fatty acid - 0.004kg, 16KJ
Plasma triacylglycerol, 0.004kg, 160 KJ
Adipose tissue - 12kg, 40,400KJ
Intramuscular triacylglycerol - 0.3kg, 10,800 KJ
What happens when you go over 65%-80% of VO2 max?
Before that use carbs and fats equally
After that fats drops massively and carbs is increased
What are the possible limitations to fat oxidation during exercise?
Want fatty acids that can be transported to the muscle for fuel
These are made from lipoprotein lipase breaking triglycerides, or Adrenaline released by exercise causing lipolysis through hormone sensitive lipase causing triglycerides to turn into fatty acids
Increase in insulin (released after a meal) causes lipogenesis, fatty acids turned into triglycerides
Problem is actually that fewer fats actually being able to get into the muscle cell - even though the supply of fats is enough
The ability of the cell to take them up is not actually impaired, so the decline must be intracellular
Co enzyme A exists in small amounts in the cytosol and mitochondria to form Acyl-CoA, but it is also needed for beta oxidation of Acyl-CoA to Acetyl-CoA
Co enzyme A also needed in the carbohydrate pathway, when this increases so does this demand
Same problem with Carnitine which takes Acyl-CoA across the mitochondrial membrane, it is also required on the carbohydrate side to form acetlycarnitine
The more trained we get do we utilise fat more?
yes. it enhances fat oxidation
What is Fatmax?
Where fat oxidation peaks
Around 50-65% achten et al 2002
Does fat oxidation increase with exercise duration (fasted state)?
yes
What can a nutritionist potentially do?
Increase endogenous fat availability, increasing fat oxidation and spare carbohydrate - good for performance
Can we increase this in the diet and should we?
What happens when pre exercise fat feeding (+heparin which helps them to be converted to fatty free acids) occurs?
Increases fat oxidation, and spares muscle glycogen use
Without heparin does not help, as only triglyceride levels have increased as not being converted quickly to fatty free acids
Overall pre exercise fat feeding does not help exercise performance
Take home points on acute fat feeding?
It’s not easy to increase fatty acid availability
When increased you do increase fatty acid oxidation
This doesn’t help with exercise performance
Regardless of the length of chain of fat feeding
Why doesn’t it help? and if supplementing is not possible can chronic feeding be used as a practical strategy
3 day high fat diet on cyclists has what effect?
Favourable changes in substrate use with high fat diet
They have adapted to be able to utilise fat more effectively
Does more fat in diet result in more optimal storage of intramuscular triglyceride stores and glycogen stores?
No, need a set amount in the diet to maintain IMTG stores, and too much and impair glycogen storage
Does a low fat diet result in more glycogen utilisation?
yes
Over 7 weeks what improved cycling performance more, the high carb or high fat diet?
High carb by far.
Baseline knowledge on low fat intake and high fat intake?
If too low:
There is progressive depletion of IMTG
Minimum fat intake is required to maintain IMTG stores ( a key energy source for endurance performance)
If too high:
Results in greater fat oxidation
Also results in lower muscle glycogen storage
This reduces performance, particularly during higher intensity events which rely on carbohydrate oxidation
This could also be due to a decrease in the efficiency of CHO use during more intense exercise
A theory on how to get the best out of both high CHO diet and high Fat diet?
Have people of high fat diet in weeks leading up to performance so adapt to be able to perform more fat oxidation
Then before performance have a high CHO diet to replenish glycogen stores
Because:
Potentially elevated ketones are shown that they increase RPE
High fat diet make it difficult to reach a ‘top gear’, as their ability to move carbohydrate through the rate limiting step of pyruvate dehydrogenase is reduced
The high fat diet has deprimed the carbohydrate adaptations the body has
Conclusions on should you have a high fat diet or high carb diet?
High carb is better, good endurance exercise is also normally performed higher than 75% VO2 max as this is strongly CHO dependant
So under most conditions Fat adaptation is not useful for exercise performance
Caffeine mechanisms to improve exercise performance?
Blood:
Increased free fatty acids, means less carbohydrate stores used
Muscle:
Altered {K+}
Blood lactate concentration
Increasing Ca handling = increasing the power of muscle contractions
Brain:
Increased motor unit recruitment
Adenosone antagonism = decreased rpe and pain
Increases reaction time, alertness and mood = anti fatigue effects
What are the factors that limit repeated sprint performance?
Phosphocreatine supply
Low muscle pH - acidosis
Extracellular potassium accumulation - altered excitability
Central fatigue
How much ATP do we produce a day?
Our body weight
If very active can double;e or triple
Why do we care about the integration of fuel metabolism?
The integration of fuel metabolism is crucial to generating large amounts of ATP
Important in the current day
What do we mean by the intergration of fuel metabolism?
At any time point the energy required by the cells of our body (metabolic rate) is almost always provided by both fat and CHO utilisation
Different circumstances can require different amounts of energy
At any given energy expenditure there can be a different contribution of dat and CHO to this energy expenditure
Importance of skeletal muscle in fuel metabolism?
Skeletal muscle is 40-50@ of body mass
Responsible for 20-30% of resting oxygen consumption
Mediates over 75% of all insulin mediated glucose disposal under normal physiological conditions
Primary depot for this disposal of nutrients
What’s the Randle cycle?
Fat is boss in the integration of fuel metabolism - under most conditions it’s what regulates metabolism over carbohydrates
Fatty-acid pathway can inhibit the glucose pathway
The acceleration of fat metabolism happens over carbs when we are fasting
End product inhibition, fatty acid cycle produces Acetyl-CoA, which is also the end product of glucose metabolism, so if the glucose pathway isn’t even working hard there is an imbalance between pyruvate which should be converted into the abundant acetyl-CoA which has now been made harder
Acetyl-CoA also enters the TCA cycle and one of the products it produces is Citrate, which in excess diffuses across the mitochondrial membrane into the cytosol, where it inhibits phospofructokinsase, and essential enzyme is glycolysis
This results in a build up of glucose-6-phosphate, which inhibits hexokinase which is required to activate the glucose molecule
Empirical data supports all of this
Empirical evidence supporting the randle cycle?
Increasing plasma FFA (via lipid and heparin infusion):
(Odland et al, 1998, 2000).
• Suggests regulation at PFK.
33% ↓ thigh glucose uptake during moderate intensity knee extensor exercise
(Hargreaves et al, 1991).
• Suggests regulation at GLUT4.
↑ fat oxidation by 15% and ↓glycogenolysis by 50% at >80% VO2max. ↔ PDC activity and muscle contents of acetyl-CoA, citrate, and G-6-P. ↓ free ADP and AMP. (Dyck et al, 1993, 1996; Romijn et al, 1995).
• Suggests regulation at Glycogen phosphorylase.
Insulin stimulated glucose uptake?
Eat carbs meal
Carbs digested and absorbed as glucose which is distributed in circulation
As glucose passes by the pancreas, pancreatic beta cells release insulin
Glucose is impermeable so needs an active transporter (insulin)
More simple carbs = quick insulin peak (easier to breakdown)
More complex carbs = more prolonged peak (harder to breakdown)
Insulin attached to insulin receptor on cell membrane
Phosphorylation and therefore activation of IRS-1
IRS-1 stimulates PI3kinase, this stimulates GLUT4 (a muscle specific transporter) to go from vesicles within the cell into the cell membrane
PI3kinase also stimulates the protein AKt, which stimulates GLUT4 as well
GLUT4 makes the cell membrane essentially permeable to glucose
Akt also directly regulates the pyruvatedehydrogenase complex
3 routes the initial glucose molecule can take?
Aerobically converted from pyruvate into acetyl-CoA
Anaerobically converted from Pyruvate into lactate
Stored as glycogen
Does the feeding of glucose ( so not being in a fasted state) disrupt the randle cycle?
Yes, it helps to reverse the randle cycle
But it only impairs oxidation of long chain fatty acids, not medium chain
This switch is controlled by CPT1
Molecular mechanism how the fed state reverses the randle cycle?
Rise in glucose results in an increase Acetyl-CoA
Produced in excess to what the TCA cycle can handle
So it is converted by the ACC enzyme into Malonyl-CoA which inhibits CPT1
Data saying that malonyl-CoA is not involved?
> 2fold ↑ in fat oxidation (due to depleted pre-exercise muscle glycogen content) during exercise at 65% VO2,peak. ↔ muscle malonyl-CoA compared to control.
(Roepstorff et al, 2005)
No association between muscle malonyl-CoA content and fat oxidation rates during
prolonged moderate-intensity exercise or graded-intensity exercise. (Odland et al, 1996, 1998; Dean et al, 2000)
so doesn’t work in humans
Free carnitine hypothesis?
Acetyl-CoA converted into acetylcarnitine and moved into the cytosol by CAT and CACT reacting acetyl-CoA and Carnitine
Acetyl-CoA can act as a metabolic sink
CoA is also produced which can be used by the mitochondria
This overall causes a decrease in free Carnitine, so can’t act as a cofactor for CPT1 to shuttle fatty acids (acetyl-CoA) into the mitochondria -this is the limiting step everyone believes right now
Claims around carnitine supplementation?
Broad et al. (2005) found no effect of oral L-carnitine supplementation for 4 weeks (3g/day) on carbohydrate and fat metabolism or on exercise performance
Vukovich et al. (1994) reported no significant effects on fat or carbohydrate metabolism during exercise at 70% VO2max after 14 days (6g/day) supplementation of L-carnitine.
Wächter et al. (2002) also concluded that oral L-carnitine supplementation for 3 months (4g/day) did not affect exercise performance.
Importantly, Wächter et al. (2002) and Vukovich et al. (1994) reported that L- carnitine supplementation did not alter muscle carnitine content.
Does not work from these studies, it works basically only in the muscle, so when you digest it there is an unfavourable concentration to get more in the muscle
So you need molecules that bring the carnitine into the muscle, can use carbohydrates to do this
Ben wall and colleagues shows it can work when it is up taken, can alter fat and carb oxidation, and can increase exercise performance by saving glycogen stores through driving fat oxidation (only lower intensities), but at higher % of Vo2 max where carnitine is a limiting factor for fat oxidation, it didn’t actually help, what it did was reduce lactate accumulation
What carnitine did was change its role from being used in CPT1 translation to the mitochondria, or it’s role as a acetyl buffer depending on glycolytic flux
So higher glycolytic flux (higher work intensity) drove carnitine to help form a metabolic sink for acetyl coA, more of it means it can be done in larger quantities, reducing pyruvate quantities and therefore lactate accumulation
What is insulin resistance?
The reduced responsiveness of skeletal muscle glucose uptake to normal circulating levels of insulin
Can also be viewed as…
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.
Makes it harder to get glucose into the cell, therefore results in it being harder to use it to generate energy
Some techniques at measuring insulin resistance?
Single blood sample
Ratio of insulin to glucose in your blood using an equation
Healthy in fasted = low in both
Diabetes type 2 = high insulin and high glucose as it just isn’t enough to get the glucose in the cell
Or high glucose low insulin, as the pancreas has been stimulated so much it can’t release much anymore
One technique is looking at glucose disposal rate
Gold standard is hyperinsulianemic clamp technique
Measuring insulin resistance, the hyperinsulianemic clamp technique?
Induce artificial high levels of insulin pumped into the body
Glucose chased away into peripheral cells, so you inject glucose as well and look at the rate in which it gets put into cells
Athlete will have fast rate
Obese will have slow rate
Features of type 2 diabetes and insulin resistance?
Insulin resistance is usually brought about by increased energy intake, physical inactivity and/or the development of being overweight and/or obese.
Insulin resistance is the direct precursor to frank type 2 diabetes.
Type 2 diabetes is defined as resulting from a defect in both insulin sensitivity and
80% of type 2 diabetics are obese
2.75 million people in the UK now have diabetes, 2 million of which have type 2 diabetes. The total is forecast to climb to four million by 2025.
Diabetes accounts for approximately a tenth of NHS budget each year, a total exceeding £9 billion.
The complications of diabetes are numerous and include amputation, heart disease, kidney failure and blindness.
What is metabolic inflexibility?
Obese people suffer from it
From fasting to insulin stimulated they can’t oxidise the glucose they have digested
Can’t switch between fat and carb oxidation
Lipid overspill theory (following on from Randle cycle)?
Big lipid droplets form in muscle
Broken down to acyl-CoA
Athlete can turn these over
Obese can’t, resulting in an accumulation of fatty acid intermediates, such as Ceramide and Diacylglycerol
These stimulate the JNK pathway which can directly inhibit the IRS-1 which is needed for to pathway of insulin creating an effect within the muscle cell
The IkKB and PKC pathways do the same to IRS-1
Overall this exacerbates the cycle build up of lipids
What’s the inflammation theory?
Excess lipid and adipose tissue release Il-6 and TNF-a cytokines can interfere with insulin signalling
Interacts with JNK pathway as well
What can’t obese individuals oxidise?
Muscle and plasma triglyceride
Can do endogenous carbohydrate and plasma FFA
When we do exercise without insulin being present (haven’t just had a meal) is glucose still used?
yes, so it is contraction stimulated glucose uptake
Contraction increases concentration of Ca2+
and turns ATP broken down into AMP and ADP, this changes the charge of the cell, this ratio tells AMPK what to do
AMP accumulates, AMPK tells the cell to breakdown Glycogen to provide ATP
AMPK also tells GLUT4 to go to the membrane, and stimulates CPT1 to shuttle fats into the mitochondria
Ca2+ increase stimulates PDC increase activity, as well as the enzyme CaMK which increases GLUT4 translocation the cell membrane
Does exercise increase insulin sensitivity in obese individuals?
yes
Type 2 diabetes pharmacological approaches?
Secretagogoues:
Sulphonylureas
Meglinitinides
Exogenous insulin
Sensitisers:
Biguanides
Thiazoliddinediones
AICAR
Peptide analogous/agonists
Exenatide
These work at the metabolic level to increase metabolism
What are proteins?
Chain (polymer) of amino acids
Arranged into primary, secondary and tertiary (and quaternary) structures
Contain Nitrogen
How are proteins made?
Transcription
Translation (initiation, elongation, termination)
Post translational modification
What do proteins do?
Provide structure Hormones Antibodies Transporters Enzymes Movement
(muscle) protein synthesis?
The creation of new proteins from amino acids (as a result of initial transcription of the DNA)
(muscle) protein breakdown?
The degradation of whole proteins back to constituent amino acids
(Muscle) protein balance?
The net result of muscle protein synthesis and muscle protein breakdown (synthesis -breakdown)
Amino acid oxidation?
The breakdown of intracellular amino acids for energy production
If oxidised not available for protein synthesis
Amino acid uptake?
The rate of transport of amino acids from one pool (eg. the plasma) to antlers (e.g. the muscle cell)
Amino acid utilization?
The amount of dietary amino acids (obtained from dietary protein) that is used by the tissue and organs of the body for the above processes
