S10 Metabolic and Endocrine Control during Special Circumstances Flashcards
What fuel sources are normally available in the blood?
Glucose (stored as glycogen in liver and skeletal muscle)
Fatty acids (stored at TAG in adipose tissue)
Which fuel sources are availed under special conditions?
Amino acids - converted to glucose or ketone bodies
Ketone bodies - from fatty acids - brain can use this
Lactate - product of anaerobic metabolism in muscle - can be converted back into glucose in the Cori cycle by liver or utilised for TCA cycle by other tissues
What are the anabolic hormones involved in metabolic control?
Insulin
And growth hormone in terms of the fact it increases protein synthesis
What are the catabolic hormones involved in metabolic control?
- glucagon
- adrenaline
- cortisol
- growth hormone - increases lipolysis and gluconeogenesis
- thyroid hormones
Which metabolic processes does insulin lead to the inhibition of?
- gluconeogenesis
- glycogenolysis
- lipolysis
- ketogenesis
- proteolysis
Which metabolic processes does insulin lead to the activation of?
- glucose uptake in muscle and adipose (GLUT4)
- glycolysis
- glycogen synthesis
- protein synthesis
What metabolic processes occur in energy starvation?
- Reduction of blood glucose stimulates the release of cortisol from the adrenal cortex and glucagon from the pancreas
- These stimulate gluconeogenesis and fat and protein breakdown
- Reduced insulin levels and anti-insulin effects of cortisol prevent cells from using glucose - fatty acids are metabolised instead
- The liver starts producing ketone bodies and the brain utilise these instead of glucose
- The kidneys start to contribute to gluconeogenesis
- When fat stored are depleted, protein is used as fuel
- If death occurs, it is because of loss of muscle mass
Why must increase in protein content of diet be gradual if someone is malnourished?
Otherwise get refereeing syndrome (ammonia poisoning)
What are the two main phases of metabolic adaptation during pregnancy?
- anabolic phase - predatory increase in maternal nutrient stores especially adipose
- catabolic phase - maternal metabolism adapts to meet an increasing demand by fetal-placental unit
What happens in the anabolic phase of pregnancy?
- increase in maternal fat stores
- small increase in insulin sensitivity
- nutrients are stored to meet future demands of rapid fetal growth and lactation after birth
This is early pregnancy
What happens in the catabolic phase of pregnancy?
- decreased insulin sensitivity/increased insulin resistance - increase in maternal glucose and free fatty acid concentration - more substrate available for fetal growth
- maternal tissues use fatty acids instead of glucose
Occurs in late pregnancy
What happens in placental transfer?
Most substances are transferred by simple diffusion down concentration gradients
- glucose transfer is by facilitated diffusion via GLUT1 transporters
What is a fetoplacental unit?
In pregnancy, the placenta, fetal adrenal glands and fetal liver control maternal metabolism to ensure the fetus’ survival.
The placenta secretes lots of proteins that can control the maternal hypothalamic pituitary axi
What are anti-insulin hormones in pregnancy? What is the effect on the mother?
Hormones secreted by the placenta that have anti-insulin effects on the maternal metabolism
E.g. corticotropin releasing hormone, human placental lactogen, progesterone
Transient hyperglycaemia after meals due to increases insulin resistance
But hypoglycaemia can occur between meals and at night due to continuous fetal draw of glucose
What effect do oestrogens and progesterone have on pancreatic beta-cells?
They increase the sensitivity of maternal pancreatic beta-cells to blood glucose - so increased insulin synthesis and secretion.
- if the beta-cells don’t respond normally, blood glucose can become very high and gestational diabetes can develop
What is gestational diabetes?
A disease in which pancreatic beta-cells don’t produce enough insulin to meet the increased requirement in late pregnancy
What are 3 underlying causes of gestational diabetes?
- autoantibodies similar to those of type 1 diabetes mellitus
- genetic susceptibility similar to maturity onset diabetes (rare)
- beta-cell dysfunction linked to obesity and chronic insulin resistance e.g. evolving type 2 diabetes mellitus - common
What are the clinical implications of gestational diabetes?
- increases risk if miscarriage
- increases risk of congenital malformation
- fetal macrosomia can occur - large bodied baby
- disproportionate amount of adipose around the shoulders and chest - shoulder dystocia - shoulders could get stuck during birth
- gestational hypertension and pre-eclampsia
These can reduced if it is diagnosed and managed
What plays a role in determining if a women’s develops gestational diabetes or not?
Their starting point in terms of insulin resistance before pregnancy
Risk factors:
- maternal age over 25 years
- BMI of 25kg/m2 or above
- more common in Asian, black and Hispanic ethnic groups
- personal/family history of diabetes
- family history of macrosomia
How do you manage gestational diabetes?
- dietary modification
- insulin injection
- regular ultrasounds to assess the fetal growth and wellbeing
In which body systems are there rapid adaptations when someone goes from rest to exercise?
- MSK
- CVS
- respiratory system
- temperature regulation
When someone is exercising, what does the metabolic response need to ensure?
- increased energy demands of skeletal and cardiac muscle are met by mobilisation of energy stores
- there are minimal disturbances to metabolic homeostasis - keep rate of mobilisation = to rate of utilisation
- glucose supply to the brain is maintained
- the end products of metabolism are removed ASAP
What needs to be rapidly resynthesised to meet metabolic demands on cells during exercise?
ATP
Where does the energy come from used in exercise?
- muscle creatine phosphate stored can quickly replenish ATP
- glycolysis
- oxidation phosphorylation
How is muscle glycogen used in intensive exercise and low intensity exercise?
- short intensive can be sustained by breakdown of muscle glycogen
- long low intensive - enough oxygen can be supplied for complete oxidation of glucose and glycogen stored (muscle and liver)
Muscle glycogen (glycogen phosphorylase) —> G-6-P —> glycolysis (PFK)—> pyruvate (if aerobic, enters TCA cycle) —> lactate (if anaerobic)
How is lactate removed?
By the cori cycle in the liver - lactate is recycled reproducing glucose
1x glucose in the liver —> glucose in the muscle —> 2x lactate in the muscle —> 2x lactate travels in the blood to the liver where it is converted back into 1x glucose
How do muscles take up blood glucose?
Via GLUT4 and GLUT1 transporters
What is the insulin independent process of glucose uptake in exercising muscles?
An increase in AMP stimulates AMPK (AMP activated protein kinase) which results in a signalling cascade which increased GLUT4 translocation to plasma membrane
How is fatty acid used as a fuel in exercise?
- can only be used in aerobic conditions
- slow release from adipose tissue
- limited carrying capacity in blood
- it’s capacity is limited by uptake across the mitochondrial membrane by the carnitine shuttle
It has a low rate of ATP production but a high capacity for sustained production
What energy stores are used in a 100m sprint?
- anaerobic
- lactate produced, H+ build up, fatigue
- uses muscle store of glycogen
What energy stores are used in 1500m middle distance?
- some oxygen can be delivered to muscles so both aerobic and anaerobic
- aerobic metabolism can use glucose and fatty acids
- Start uses creatine phosphate and anaerobic glycogen metabolism
- Middle phase, ATP is produced aerobically from muscle glycogen (need oxygen supply to muscles)
- Finish sprint relies on anaerobic metabolism of glycogen, lactate is produced
What energy stores are used in a marathon?
- mostly aerobic
- used muscle glycogen, liver glycogen and fatty acids
- the muscle glycogen is depleted in few mins, glucose from liver glycogen peaks at an hour then declines, fatty acid utilisation rises from 20-30mins in
What is the order of store utilisation during exercise over time?
- ATP and creatine phosphate
- Anaerobic glycolysis - muscle glycogen
- Aerobic oxidation - muscle glycogen, plasma glucose and liver glycogen
- Aerobic oxidation - plasma free fatty acids and adipose tissue TAGs
What happens to hormone levels in response to prolonged exercise?
- insulin levels fall (slowly) - inhibited by adrenaline
- glucagon levels rise - glycogenolysis, gluconeogenesis and lipolysis
- adrenaline and growth hormone levels rise (quickly) - glycogenolysis and lipolysis (adrenaline) and gluconeogenesis (growth hormone)
- cortisol levels rise (slowly) - lipolysis and gluconeogenesis
What enzyme is activated by glucagon stimulating glycogenolysis?
Glycogen phosphylase
Which enzymes are activated by glucagon stimulating gluconeogenesis?
PEPCK and fructose-1,6-bisphosphate
What enzyme is activated by glucagon stimulating lipolysis?
Hormone sensitive lipase
What are the benefits of exercise?
- body composition changes - more muscle, less fat
- glucose tolerance improves
- insulin sensitivity of tissues increases
- blood TAGs decrease (increase in HDL, decrease in VLDL and LDL)
- blood pressure falls
^ all important for diabetics - psychological effects
